1
|
Mahmoudi Gharehbaba A, Soltanmohammadi F, Vandghanooni S, Eskandani M, Adibkia K. A comprehensive review on overcoming the multifaceted challenge of cancer multidrug resistance: The emerging role of mesoporous silica nanoparticles. Biomed Pharmacother 2025; 186:118045. [PMID: 40215648 DOI: 10.1016/j.biopha.2025.118045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2024] [Revised: 03/26/2025] [Accepted: 04/03/2025] [Indexed: 04/25/2025] Open
Abstract
Multidrug resistance (MDR) is a significant challenge in tumor treatment, severely reducing the effectiveness of anticancer drugs and contributing to high mortality rates. This article overviews the various factors involved in the development of MDR, such as changes in drug targets, increased DNA repair mechanisms, and the impact of the tumor microenvironment. It also emphasizes the potential of mesoporous silica nanoparticles (MSNs) as a drug delivery system to combat MDR. With their unique characteristics-such as a high surface area, adjustable pore sizes, and the ability to be functionalized for targeted delivery-MSNs serve as excellent carriers for the simultaneous delivery of chemotherapeutics and siRNAs aimed at reversing resistance pathways. The paper focuses on innovative methods using MSNs for direct intranuclear delivery of their cargos to overcome efflux barrier and improve the effectiveness of combination therapies. This review highlights a promising approach for enhancing cancer treatment outcomes by integrating advanced nanotechnology with traditional therapies, addressing the ongoing challenge of MDR in oncology.
Collapse
Affiliation(s)
- Adel Mahmoudi Gharehbaba
- Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Fatemeh Soltanmohammadi
- Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Somayeh Vandghanooni
- Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Morteza Eskandani
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Khosro Adibkia
- Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
| |
Collapse
|
2
|
Erdemir-Cilasun G, Özerkan D, Kariper İA, Sert E, Korkut IN, Danışman-Kalındemirtaş F. Improved apoptosis and mitochondrial dysfunction: the potential of carmofur-platinum nanoparticles. Biomed Mater 2025; 20:035024. [PMID: 40216001 DOI: 10.1088/1748-605x/adcbfa] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Accepted: 04/11/2025] [Indexed: 04/24/2025]
Abstract
Despite their impact on cancer therapy, limitations such as systemic toxicity and drug resistance are encountered with platinum-based drugs. This study explores the potential of combining PtIV-based NP with carmofur (Car) to address these issues. In this study, platinum nanoparticles (PtNPs) and Car-loaded PtNP (Car@PtNP) were synthesized and their cytotoxic and apoptotic effects on colorectal and breast cancer cells were evaluated. Following characterization of the synthesized NPs by dynamic light scattering, UV-VIS spectroscopy, FTIR, and STEM, it was found that the average size of PtNPs was 55.42 nm and the size increased to approximately 186.06 nm upon synthesis of Car@PtNP. MTT assays demonstrated that Car@PtNP exhibited higher levels of cellular toxicity than carmofur alone. While it significantly decreased cell viability in both colon and breast cancer cells, its toxicity to HUVEC cells was minimal. Treatment of MCF-7 and HCT116 cells with 50 µg ml-1of free Car resulted in cell viabilities of 65.2% and 76.93%, respectively, whereas the viability of cells treated with Car@PtNP decreased to 49.60% and 55.47%. Flow cytometric analysis confirmed that apoptosis was increased in healthy HCT116 cells treated with Car@PtNP, with a marked increase in both early and late apoptotic cell populations. Furthermore, these results were confirmed by Hoescht and Rhodamin123 immunofluorescence staining, and significant mitochondrial dysfunction and apoptotic morphological changes were observed in treated cells. The findings underscore the promise of Car@PtNP as a novel chemotherapeutic approach, integrating the benefits of PtIVcomplexes and Car to enhance antitumor efficacy while mitigating the drawbacks of conventional platinum-based therapies.
Collapse
Affiliation(s)
- Gökçe Erdemir-Cilasun
- Department of Medical Biology, Faculty of Medicine, Biruni University, Istanbul, Turkey
| | - Dilşad Özerkan
- Department of Genetic and Bioengineering, Faculty of Engineering and Architecture, Kastamonu University, 37150 Kastamonu, Turkey
| | - İshak Afşin Kariper
- Department of Science Education, Education Faculty, Erciyes University, 38039 Kayseri, Turkey
| | - Esra Sert
- Department of Hematology, Istanbul Faculty of Medicine, Istanbul University, 34390 Istanbul, Turkey
| | - Işık Neslişah Korkut
- Department of Physiology, Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, Turkey
| | | |
Collapse
|
3
|
Zhou Y, Camisasca A, Dominguez-Gil S, Bartkowski M, Rochfort KD, Piletti M, White A, Krizsan D, O'Connor R, Quinn SJ, Iacopino D, Eustace AJ, Giordani S. Synthesis of carbon dots from spent coffee grounds: transforming waste into potential biomedical tools. NANOSCALE 2025; 17:9947-9962. [PMID: 40067158 DOI: 10.1039/d4nr05186f] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/18/2025]
Abstract
Carbon dots (CDs) are small-sized, spherical nanoparticles presenting amorphous carbon cores with nanocrystalline regions of a graphitic structure. They show unique properties such as high aqueous solubility, robust chemical inertness, and non-toxicity and can be manufactured at a relatively low cost. They are also well known for outstanding fluorescence tunability and resistance to photobleaching. Together, these properties boost their potential to act as drug delivery systems (DDSs). This work presents a low-cost synthesis of CDs by upcycling spent coffee grounds (SCGs) and transforming them into value-added products. This synthetic route eliminates the use of highly toxic heavy metals, high energy-consuming reactions and long reaction times, which can improve biocompatibility while benefiting the environment. A series of physico-chemical characterisation techniques demonstrated that these SCG-derived CDs are small-sized nanoparticles with tunable fluorescence. In vitro studies with 120 h of incubation of SCG-derived CDs demonstrated their specific antiproliferative effect on the breast cancer CAL-51 cell line, accompanied by increased reactive oxygen species (ROS) production. Importantly, no impact was observed on healthy breast, kidney, and liver cells. Confocal laser scanning microscopy confirmed the intracellular accumulation of SCG-derived CDs. Furthermore, the drug efflux pumps P-glycoprotein (P-gp) and the breast cancer resistance protein (BCRP) did not impact CD accumulation in the cancer cells.
Collapse
Affiliation(s)
- Yingru Zhou
- School of Chemical Science, Dublin City University, Glasnevin, Dublin, Ireland.
- Life Sciences Institute, Dublin City University, Glasnevin, Dublin, Ireland.
| | - Adalberto Camisasca
- School of Chemical Science, Dublin City University, Glasnevin, Dublin, Ireland.
| | - Sofia Dominguez-Gil
- School of Chemical Science, Dublin City University, Glasnevin, Dublin, Ireland.
| | - Michał Bartkowski
- School of Chemical Science, Dublin City University, Glasnevin, Dublin, Ireland.
| | - Keith D Rochfort
- Life Sciences Institute, Dublin City University, Glasnevin, Dublin, Ireland.
- School of Biotechnology, Dublin City University, Glasnevin, Dublin, Ireland
| | - Martina Piletti
- Tyndall National Institute, University College Cork, Cork, Ireland
| | - Anita White
- Life Sciences Institute, Dublin City University, Glasnevin, Dublin, Ireland.
- School of Biotechnology, Dublin City University, Glasnevin, Dublin, Ireland
| | - Dorottya Krizsan
- School of Chemistry, University College Dublin, Belfield, Dublin, Ireland
| | - Robert O'Connor
- School of Physical Sciences, Dublin City University, Glasnevin, Dublin, Ireland
| | - Susan J Quinn
- School of Chemistry, University College Dublin, Belfield, Dublin, Ireland
| | - Daniela Iacopino
- Tyndall National Institute, University College Cork, Cork, Ireland
| | - Alex J Eustace
- Life Sciences Institute, Dublin City University, Glasnevin, Dublin, Ireland.
- School of Biotechnology, Dublin City University, Glasnevin, Dublin, Ireland
| | - Silvia Giordani
- School of Chemical Science, Dublin City University, Glasnevin, Dublin, Ireland.
- Life Sciences Institute, Dublin City University, Glasnevin, Dublin, Ireland.
| |
Collapse
|
4
|
Zaman A, Das PK. Transferrin Tethered Fluorescent Organic Nanoparticles for Receptor-Mediated Targeted Delivery of Paclitaxel to Cancer Cells. Chem Asian J 2025:e202500135. [PMID: 40195826 DOI: 10.1002/asia.202500135] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2025] [Revised: 03/13/2025] [Accepted: 03/24/2025] [Indexed: 04/09/2025]
Abstract
Cancer remains a critical global issue, marked by its high mortality rates. Despite achieving remarkable progress in cancer treatments, conventional chemotherapeutic drugs face numerous limitations. To this end, nanomaterial-based targeted drug delivery systems have emerged as a hope of promise. In this study, we report the design and development of transferrin (Tf) tethered naphthalene-diimide-based fluorescent organic nanoparticles (NDI-OH-Tf) for targeted delivery of paclitaxel to cancer cells with over expressed transferrin receptors (TfR). Spherical NDI-OH FONPs were fabricated through J-type of aggregation of NDI-OH amphiphiles in a 1:99 (v/v) DMSO-H2O mixture. These NDI-OH FONPs exhibited aggregation induced emission (AIE) at an emission wavelength of λem = 594 nm. The hydroxyl groups on the surface of the NDI-OH FONPs were conjugated with carboxyl groups of transferrin, forming NDI-OH-Tf FONPs. These NDI-OH-Tf FONPs were successfully used for targeted bioimaging and drug delivery to TfR+ cancer cells through ligand receptor interaction between transferrin and TfR. Notably, paclitaxel loaded NDI-OH-Tf exhibited ∼2.9-fold higher efficacy toward TfR+ cancer cells compared to normal cells and ∼3.3-fold higher cytotoxicity than free PTX due to transferrin mediated targeted accumulation of PTX in cancer cells.
Collapse
Affiliation(s)
- Afreen Zaman
- School of Biological Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700 032, India
| | - Prasanta Kumar Das
- School of Biological Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata, 700 032, India
| |
Collapse
|
5
|
Tiwade PB, Fung V, VanKeulen-Miller R, Narasipura EA, Ma Y, Fenton OS. Non-Viral RNA Therapies for Non-Small Cell Lung Cancer and Their Corresponding Clinical Trials. Mol Pharm 2025; 22:1752-1774. [PMID: 40131145 DOI: 10.1021/acs.molpharmaceut.4c00871] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/26/2025]
Abstract
Ribonucleic acid (RNA)-based therapies represent a promising class of drugs for the treatment of non-small cell lung cancer (NSCLC) due to their ability to modulate gene expression. Therapies leveraging small interfering RNA (siRNA), messenger RNA (mRNA), microRNA (miRNA), and antisense oligonucleotides (ASOs) offer various advantages over conventional treatments, including the ability to target specific genetic mutations and the potential for personalized medicine approaches. However, the clinical translation of these therapeutics for the treatment of NSCLC faces challenges in delivery due to their immunogenicity, negative charge, and large size, which can be mitigated with delivery platforms. In this review, we provide a description of the pathophysiology of NSCLC and an overview of RNA-based therapeutics, specifically highlighting their potential application in the treatment of NSCLC. We discuss relevant classes of RNA and their therapeutic potential for NSCLC. We then discuss challenges in delivery and non-viral delivery strategies such as lipid- and polymer-based nanoparticles that have been developed to address these issues in preclinical models. Furthermore, we provide a summary table of clinical trials that leverage RNA therapies for NSCLC [which includes their National Clinical Trial (NCT) numbers] to highlight the current progress in NSCLC. We also discuss how these NSCLC therapies can be integrated with existing treatment modalities to enhance their efficacy and improve patient outcomes. Overall, we aim to highlight non-viral strategies that tackle RNA delivery challenges while showcasing RNA's potential as a next-generation therapy for NSCLC treatment.
Collapse
MESH Headings
- Humans
- Carcinoma, Non-Small-Cell Lung/therapy
- Carcinoma, Non-Small-Cell Lung/genetics
- Carcinoma, Non-Small-Cell Lung/drug therapy
- Lung Neoplasms/genetics
- Lung Neoplasms/therapy
- Lung Neoplasms/drug therapy
- RNA, Small Interfering/genetics
- RNA, Small Interfering/therapeutic use
- RNA, Small Interfering/administration & dosage
- Oligonucleotides, Antisense/therapeutic use
- Oligonucleotides, Antisense/genetics
- Oligonucleotides, Antisense/administration & dosage
- Clinical Trials as Topic
- Animals
- Nanoparticles/chemistry
- MicroRNAs/genetics
- MicroRNAs/therapeutic use
- RNA, Messenger/genetics
- Genetic Therapy/methods
- Drug Delivery Systems/methods
Collapse
Affiliation(s)
- Palas Balakdas Tiwade
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Vincent Fung
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Rachel VanKeulen-Miller
- Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Eshan Amruth Narasipura
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Yutian Ma
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| | - Owen S Fenton
- Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, United States
| |
Collapse
|
6
|
Kaur C, Villarreal E, Cabe MH, Langert KA. Blood nerve barrier permeability enables nerve targeting of circulating nanoparticles in experimental autoimmune neuritis. Sci Rep 2025; 15:11763. [PMID: 40189681 PMCID: PMC11973151 DOI: 10.1038/s41598-025-96231-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Accepted: 03/25/2025] [Indexed: 04/09/2025] Open
Abstract
Guillain-Barré syndrome (GBS) is a devastating autoimmune disease of the peripheral nervous system (PNS) with limited treatment options. Several studies have shown attenuation of the well-characterized GBS preclinical experimental autoimmune neuritis (EAN) model with systemically administered therapeutic compounds via anti-inflammatory or immunomodulatory mechanisms. Despite this, clinical advancement of these findings is limited by dosing that is not translatable to humans or is associated with off-target and toxic effects. This is due, in part, to the blood-nerve barrier (BNB), which restricts access of the circulation to peripheral nerves. However, during acute neuroinflammation, the normally restrictive BNB exhibits increased vascular permeability and enables immune cell infiltration. This may offer a unique window to access the otherwise restricted peripheral nerve microenvironment for therapeutic delivery. Here, we assessed the degree to which BNB permeability and immune cell infiltration over the course of EAN enables accumulation of circulating nanoparticles. We found that at disease stages defined by distinct clinical scores and pathology (onset, effector phase, and peak of EAN severity), intravenously administered small molecules and nanoparticles ranging from 50 to 150 nm can permeate into the endoneurium from the endoneurial vasculature in a size- and stage-dependent manner. This permeation occurs uniformly in both sciatic nerves and in proximal and distal regions of the nerves. We propose that this nerve targeting enabled by pathology serves as a platform by which potential therapies for GBS can be reevaluated and investigated preclinically in nanoparticle delivery systems.
Collapse
Affiliation(s)
- Chanpreet Kaur
- Department of Molecular Pharmacology and Neuroscience, Stritch School of Medicine, Loyola University Chicago, 2160 S. First Avenue, Bldg 115, Room 416, Maywood, IL, 60153, USA
- Research Service, Edward Hines Jr. VA Hospital, Hines, IL, 60141, USA
| | - Ellaina Villarreal
- Department of Molecular Pharmacology and Neuroscience, Stritch School of Medicine, Loyola University Chicago, 2160 S. First Avenue, Bldg 115, Room 416, Maywood, IL, 60153, USA
| | - Maleen H Cabe
- Department of Molecular Pharmacology and Neuroscience, Stritch School of Medicine, Loyola University Chicago, 2160 S. First Avenue, Bldg 115, Room 416, Maywood, IL, 60153, USA
- Research Service, Edward Hines Jr. VA Hospital, Hines, IL, 60141, USA
| | - Kelly A Langert
- Department of Molecular Pharmacology and Neuroscience, Stritch School of Medicine, Loyola University Chicago, 2160 S. First Avenue, Bldg 115, Room 416, Maywood, IL, 60153, USA.
- Research Service, Edward Hines Jr. VA Hospital, Hines, IL, 60141, USA.
| |
Collapse
|
7
|
Khot S, Mahajan U, Jadhav A, Vaishampayan P, Bagul U, Gadhave D, Gorain B, Kokare C. Nose-to-brain delivery of sorafenib-loaded lipid-based poloxamer-carrageenan nanoemulgel: Formulation and therapeutic investigation in glioblastoma-induced orthotopic rat model. Int J Biol Macromol 2025; 309:142861. [PMID: 40188927 DOI: 10.1016/j.ijbiomac.2025.142861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2024] [Revised: 03/27/2025] [Accepted: 04/03/2025] [Indexed: 04/10/2025]
Abstract
Glioblastoma multiforme (GBM) has a poor clinical prognosis, where conventional treatment offers therapeutic limitations. Therefore, the current study introduces a first-of-its-kind sorafenib (SOR) nanoemulsion (SNE) loaded with poloxamer-carrageenan nanoemulgel (SPCNEG), a novel dual-functional and natural polymer-based payload system for effective intranasal chemotherapeutic administration. The nanoformulation was developed using carrageenan (a natural gelling agent), poloxamer (a mucoadhesive agent), glyceryl caprate as lipid, and Cremophor EL:PEG 400 blend as surfactant system. The improved biopharmaceutical attributes of developed formulations were confirmed from the release experiments, revealing augmentation in drug release from SNE (84.56 ± 3.78 %) and SPCNEG (68.62 ± 4.11 %) up to 3.41- and 8.12-fold compared to plain SOR. The ex vivo experiments showed a similar enhancement in drug permeation. Moreover, the SNE also showed superior performance on glioma cell lines, as indicated by lower IC50 (2.23 μg/mL) than plain SOR (16.61 μg/mL). The pharmacokinetic study revealed a 2.52- and 3.24-fold increase in SNE and SPCNEG brain concentration, respectively, compared to Soranib®. Additionally, a high correlation was also observed between in vitro drug release and in vivo absorption at prespecified time intervals for developed formulations. In conclusion, the current research promising and non-invasive alternative to existing interventions for enhanced brain targeting potential.
Collapse
Affiliation(s)
- Shubham Khot
- Department of Pharmaceutics, Sinhgad Technical Education Society's, Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411041, Maharashtra, India
| | - Unmesh Mahajan
- Department of Pharmaceutics, Sinhgad Technical Education Society's, Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411041, Maharashtra, India
| | - Amol Jadhav
- Institute of Applied Biological Research and Development, (IABRD), A division of Nirav Biosolutions Pvt Ltd, Aundh, Pune 411007, Maharashtra, India
| | | | - Uddhav Bagul
- Department of Pharmaceutics, Sinhgad Technical Education Society's, Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411041, Maharashtra, India
| | - Dnyandev Gadhave
- Department of Pharmaceutical Science, College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, NY 11439, USA
| | - Bapi Gorain
- Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835215, Jharkhand, India
| | - Chandrakant Kokare
- Department of Pharmaceutics, Sinhgad Technical Education Society's, Sinhgad Institute of Pharmacy (Affiliated to Savitribai Phule Pune University), Narhe, Pune 411041, Maharashtra, India.
| |
Collapse
|
8
|
Shaw S, Pore SK, Liu D, Kumeria T, Nayak R, Bose S. Combating chemoresistance: Current approaches & nanocarrier mediated targeted delivery. Biochim Biophys Acta Rev Cancer 2025; 1880:189261. [PMID: 39798822 DOI: 10.1016/j.bbcan.2025.189261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 12/23/2024] [Accepted: 01/06/2025] [Indexed: 01/15/2025]
Abstract
Chemoresistance, a significant challenge in effective cancer treatment needs clear elucidation of the underlying molecular mechanism for the development of novel therapeutic strategies. Alterations in transporter pumps, oncogenes, tumour suppressor genes, mitochondrial function, DNA repair processes, autophagy, epithelial-mesenchymal transition (EMT), cancer stemness, epigenetic modifications, and exosome secretion lead to chemoresistance. Despite notable advancements in targeted cancer therapies employing both small molecules and macromolecules success rates remain suboptimal due to adverse effects like drug efflux, target mutation, increased mortality of normal cells, defective apoptosis, etc. This review proposes an advanced nanotechnological technique precisely targeting molecular determinants of chemoresistance which holds promise for enhancing cancer treatment efficacy. Further, the review explores various cancer hallmarks and pathways implicated in chemoresistance, current therapeutic modalities, and their limitations. It advocates the combination of nanoparticle-conjugated conventional drugs and natural compounds to specifically target molecular pathways that can potentially reverse or minimize chemoresistance incidences in cancer patients.
Collapse
Affiliation(s)
- Siuli Shaw
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
| | - Subrata Kumar Pore
- Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Noida, Uttar Pradesh, India
| | - Dutong Liu
- School of Materials Science and Engineering, The University of New South Wales, Sydney, NSW 2052, Australia
| | - Tushar Kumeria
- School of Materials Science and Engineering, The University of New South Wales, Sydney, NSW 2052, Australia
| | - Ranu Nayak
- Amity Institute of Nanotechnology, Amity University, Noida, Uttar Pradesh, India.
| | - Sudeep Bose
- Centre for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India; Amity Institute of Molecular Medicine and Stem Cell Research, Amity University, Noida, Uttar Pradesh, India.
| |
Collapse
|
9
|
Ben-Haim AE, Shalev N, Amalraj AJJ, Zelinger E, Mani KA, Belausov E, Shoval I, Nativ-Roth E, Maria R, Atkins A, Sadashiva R, Koltai H, Mechrez G. Nanocarriers for cancer-targeted delivery based on Pickering emulsions stabilized by casein nanoparticles. Int J Biol Macromol 2025; 298:140822. [PMID: 39929470 DOI: 10.1016/j.ijbiomac.2025.140822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2024] [Revised: 02/03/2025] [Accepted: 02/07/2025] [Indexed: 02/26/2025]
Abstract
This study demonstrates the development of stimuli-responsive Pickering emulsions stabilized by casein nanoparticles (CNPs) for targeted drug delivery to colorectal cancer cells (CRC). Encapsulation of a fluorescent dye simulates therapeutic delivery, demonstrating biomedical potential. The oil-in-water nanoemulsions stabilized by CNPs function as nanocarriers sensitive to matrix metalloproteinase-7 (MMP-7), an enzyme overexpressed in CRC cells, enabling precise drug release. Emulsions exhibited strong stability due CNPs forming a robust layer at the oil-water interface, enhancing bioavailability and controlled release. Covalent modifications of CNPs with polyethyleneimine (PEI) or polyacrylic acid (PAA), and pH adjustments optimize the zeta potential, improving surface charge and delivery efficiency. Maximal CNP uptake occurred with PAA-modified CNPs (-20 mV), showing superior interaction with CRC cells compared to pristine (-6.7 mV) and PEI-modified (+30.5, +42.1 mV) CNPs. Confocal microscopy and imaging flow cytometry confirmed that CNP-stabilized emulsions enhance CRC inter-localization compared to dispersed CNPs. Nanoemulsions with the highest CNP uptake showed selective interaction with tumor cells, while minimizing oil droplet uptake, driven by nanoscale dimensions and targeted surface interactions. Enzymatic degradation of CNPs by MMP-7 induces phase separation and targeted release. This dual-functional system, leveraging charge modification and enzymatic responsiveness, highlights CNP-stabilized nanoemulsions as a promising CRC-targeted drug delivery platform.
Collapse
Affiliation(s)
- Avital Ella Ben-Haim
- Department of Food Sciences, Institute of Postharvest and Food Sciences, Agricultural Research Organization (ARO), Volcani Institute, 68 HaMaccabim Road, Rishon Lezion 7505101, Israel; The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, POB 12, Rehovot 7610001, Israel
| | - Nurit Shalev
- Institute of Plant Sciences, Agricultural Research Organization (ARO), The Volcani Institute, PO Box 6, Beit Dagan 50250, Israel
| | - Antolin Jesila Jesu Amalraj
- Department of Food Sciences, Institute of Postharvest and Food Sciences, Agricultural Research Organization (ARO), Volcani Institute, 68 HaMaccabim Road, Rishon Lezion 7505101, Israel
| | - Einat Zelinger
- The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, POB 12, Rehovot 7610001, Israel
| | - Karthik Ananth Mani
- Department of Food Sciences, Institute of Postharvest and Food Sciences, Agricultural Research Organization (ARO), Volcani Institute, 68 HaMaccabim Road, Rishon Lezion 7505101, Israel; The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, POB 12, Rehovot 7610001, Israel
| | - Eduard Belausov
- Department of Ornamental Plants and Agricultural Biotechnology, Institute of Plant Sciences, Agricultural Research Organization (ARO), Volcani Institute, 68 HaMaccabim Road, Rishon Lezion 7505101, Israel
| | - Irit Shoval
- The Kanbar core facility unit, The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Israel
| | - Einat Nativ-Roth
- Ilse Katz Institute for Nanoscale Science and Technology, Ben Gurion University of the Negev, Israel
| | - Raquel Maria
- Ilse Katz Institute for Nanoscale Science and Technology, Ben Gurion University of the Negev, Israel
| | - Ayelet Atkins
- Institute for Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan 52900, Israel
| | - Rajitha Sadashiva
- Institute of Plant Sciences, Agricultural Research Organization (ARO), The Volcani Institute, PO Box 6, Beit Dagan 50250, Israel
| | - Hinanit Koltai
- Institute of Plant Sciences, Agricultural Research Organization (ARO), The Volcani Institute, PO Box 6, Beit Dagan 50250, Israel
| | - Guy Mechrez
- Department of Food Sciences, Institute of Postharvest and Food Sciences, Agricultural Research Organization (ARO), Volcani Institute, 68 HaMaccabim Road, Rishon Lezion 7505101, Israel.
| |
Collapse
|
10
|
Jiang S, Hao B, Song X, Jiang Y, Guo J, Wang Y, Wang Q, Wang X, Xu T, Wu X, Chan KF, Chiu PWY, Zhang L. Living Microalgae-Based Magnetic Microrobots for Calcium Overload and Photodynamic Synergetic Cancer Therapy. Adv Healthc Mater 2025; 14:e2403866. [PMID: 40012437 DOI: 10.1002/adhm.202403866] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2024] [Revised: 01/06/2025] [Indexed: 02/28/2025]
Abstract
The combination of Ca2+ overload and reactive oxygen species (ROS) production for cancer therapy offers a superior solution to the lack of specificity in traditional antitumor strategies. However, current therapeutic platforms for this strategy are primarily based on non-targeting nanomaterials, leading to undesirable off-target side effects. Additionally, resistance to ROS and apoptosis induced by the hypoxic tumor microenvironment (TME) further limits therapeutic efficiency. Herein, a magnetic microrobot based on living Spirulina Platensis (SP), which is coated with a double layer of Fe3O4 nanoparticles (NPs) and CaCO3 NPs. The microrobots can accumulate in tumor regions under magnetic attraction, which produces a high-Ca2+ environment under the acidic TME and facilitates Ca2+ overload under ultrasound (US) stimulation. Meanwhile, sufficient oxygen (O2) production by photosynthesis helps alleviate hypoxia and promotes in situ ROS production by chlorophyll-mediated photodynamic therapy (PDT), which can coordinate with Ca2+ overload to induce cell apoptosis. With these unique properties, the SP-based microrobots offer a promising microrobotics-based strategy for in situ Ca2+ accumulation and ROS production, contributing to a precise and effective way for cancer treatment.
Collapse
Affiliation(s)
- Shuai Jiang
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Bo Hao
- Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Xin Song
- Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Yihang Jiang
- Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Junjia Guo
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Yuqiong Wang
- Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Qinglong Wang
- Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Xin Wang
- Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Tiantian Xu
- Guangdong Provincial Key Laboratory of Robotics and Intelligent System, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518000, China
| | - Xinyu Wu
- Guangdong Provincial Key Laboratory of Robotics and Intelligent System, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518000, China
- SIAT Branch, Shenzhen Institute of Artificial Intelligence and Robotics for Society, Shenzhen, 518000, China
| | - Kai Fung Chan
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
- Chow Yuk Ho Technology Center for Innovative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
- Multi-Scale Medical Robotics Center, Hong Kong Science Park, Hong Kong SAR, 999077, China
- Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Philip Wai Yan Chiu
- Chow Yuk Ho Technology Center for Innovative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
- Multi-Scale Medical Robotics Center, Hong Kong Science Park, Hong Kong SAR, 999077, China
- Department of Surgery, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| | - Li Zhang
- Department of Biomedical Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
- Department of Mechanical and Automation Engineering, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
- Chow Yuk Ho Technology Center for Innovative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
- Multi-Scale Medical Robotics Center, Hong Kong Science Park, Hong Kong SAR, 999077, China
- Department of Surgery, The Chinese University of Hong Kong, Hong Kong SAR, 999077, China
| |
Collapse
|
11
|
Ailawadhi S, Pafundi D, Peterson J. Advances and future directions in radiopharmaceutical delivery for cancer treatment. Expert Rev Anticancer Ther 2025; 25:351-361. [PMID: 40019019 DOI: 10.1080/14737140.2025.2472859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2024] [Revised: 01/29/2025] [Accepted: 02/24/2025] [Indexed: 03/01/2025]
Abstract
INTRODUCTION Targeted radiopharmaceutical therapies (RPTs) have emerged as a promising approach for the precise treatment of various cancers. Delivering ionizing radiation directly to cancer cells while sparing surrounding healthy tissue, radiopharmaceuticals offer enhanced efficacy and reduced toxicity compared to conventional external beam radiation therapy (i.e. photons and electrons). AREAS COVERED In the current era of personalized cancer care, the appropriate choice of RPTs for a clinical condition and the specific patient's care needs to be better understood. Several available RPT agents with their respective clinical applicability along with rapidly ongoing research in this field have now given RPTs the ability to lend themselves to a personalized medicine focus. This review provides an overview of recent advancements in RPT, including nuclide selection and development, molecular targeting strategies, radiopharmaceutical development, and clinical applications. EXPERT OPINION We discuss the underlying principles, challenges, and opportunities for future development. Furthermore, we explore emerging technologies and future directions in the field, highlighting the potential impact on personalized cancer care.
Collapse
Affiliation(s)
| | - Deanna Pafundi
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA
| | - Jennifer Peterson
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, FL, USA
| |
Collapse
|
12
|
Wan X, Liu X, Wu P, Li Y, Shi Y, Nie Y, Zhang K, Jin Z, Song R, Zhang Z, Gan L, He J. Bioorthogonal catalytic microvesicle-mediated prodrug activation against liver cancer. J Pharm Sci 2025; 114:103774. [PMID: 40158798 DOI: 10.1016/j.xphs.2025.103774] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 03/25/2025] [Accepted: 03/25/2025] [Indexed: 04/02/2025]
Abstract
OBJECTIVE Exploring the role and mechanism of a novel bioorthogonal system using transition metals as catalysts in the treatment of hepatocellular carcinoma (HCC). METHODS Initially, a catalytic ruthenium (Ru) complex and the substrate alloc-RH 110 were synthesized, followed by the identification of their structures utilizing mass spectrometry and nuclear magnetic resonance (NMR) techniques. The catalytic efficacy of the Ru complex was then assessed using a fluorescence spectrophotometer. Subsequently, employing HepG2 cells as the cellular source, cell-derived vesicles encapsulating the Ru complexes, designated as EVs@Ru, were prepared. The EVs@Ru were characterized by measuring their particle size and Zeta potential, observing morphological features under transmission electron microscopy (TEM), and detecting specific protein expressions via Western blot analysis. Drug loading within the EVs@Ru was quantified using inductively coupled plasma mass spectrometry (ICP-MS), and their catalytic efficiency was evaluated. In vitro, the low-activity prodrug alloc-DOX was synthesized and its toxicity, along with the drug concentration in EVs@Ru, was determined. Further, the catalytic cytotoxicity of alloc-DOX against HepG2 cells encapsulated in EVs@Ru was analyzed through microscopic observation, CCK-8 assays, and apoptosis experiments. For in vivo studies, a tumor-bearing mouse model was established using human liver cancer HepG2 cells to observe the antitumor effects. Finally, the primary organs of each group of tumor-bearing mice were assessed for in vivo safety. RESULTS ESI-MS and 1H NMR confirmed the accurate structure of Ru complexes and alloc-RH 110. The Ru complexes achieved full catalytic conversion of alloc-RH 110 within 24 hours. EVs and EVs@Ru exhibited particle sizes of ∼116.85 nm and ∼281.88 nm, respectively, with Zeta potentials of ∼-20.86 mV and ∼-25.89 mV, both appearing quasi-circular under TEM. WB analysis verified the presence of vesicle-specific marker proteins in both, confirming their cell-derived nature. ICP-MS determined a drug loading of 21.90 μg/mL for EVs@Ru, with an encapsulation efficiency of ∼24.86%. Fluorescence spectrophotometry demonstrated 100% catalytic efficiency for EVs@Ru. Synthetic alloc-DOX validated by 1H NMR and ESI-MS matched literature data. MTT and CCK-8 assays confirmed low toxicity for alloc-DOX and Ru complexes, setting the experimental drug concentration at 4μM. In vitro, the EVs@Ru+alloc-DOX group exhibited potent HepG2 cell killing and apoptosis. In vivo, this group significantly inhibited tumor growth in tumor-bearing mice, with no observed toxicity to vital organs, indicating good biosafety. CONCLUSION The integration of bio-derived microvesicles (MVs) with transition metal catalysts has resulted in a biologically orthogonal system for efficient Ru complex delivery to tumor sites. This system facilitates controlled release of the Ru complexes, enabling tumor cell elimination. This innovative strategy holds great promise for enhancing tumor immunity and targeted therapeutic approaches.
Collapse
Affiliation(s)
- Xiaotian Wan
- State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Xiyu Liu
- State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Pan Wu
- State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Yongmei Li
- State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Yuanyuan Shi
- State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Yueli Nie
- State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Keyong Zhang
- State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Ze Jin
- State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Ruiyun Song
- State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning, Guangxi, 530021, China
| | - Zhikun Zhang
- State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning, Guangxi, 530021, China.
| | - Lu Gan
- State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning, Guangxi, 530021, China.
| | - Jian He
- State Key Laboratory of Targeting Oncology, National Center for International Research of Biotargeting Theranostics, Guangxi Key Laboratory of Biotargeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Talent Highland of Major New Drugs Innovation and Development, Guangxi Medical University, Nanning, Guangxi, 530021, China.
| |
Collapse
|
13
|
Al Jayoush AR, Haider M, Khan SA, Hussain Z. Hyaluronic acid-functionalized nanomedicines for CD44-receptors-mediated targeted cancer therapy: A review of selective targetability and biodistribution to tumor microenvironment. Int J Biol Macromol 2025; 308:142486. [PMID: 40139601 DOI: 10.1016/j.ijbiomac.2025.142486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 03/06/2025] [Accepted: 03/23/2025] [Indexed: 03/29/2025]
Abstract
Cancer is a leading cause of death globally, driven by late diagnoses, aggressive progression, and multidrug resistance (MDR). Advances in nanotechnology are tackling these challenges, paving the way for transformative cancer treatments. Hyaluronic acid (HA)-based nanoparticles (NPs) have emerged as promising platforms due to their biocompatibility, biodegradability, and natural targeting capabilities via CD44 (cluster of differentiation 44) receptors. Functionalizing NPs with HA enhances cellular uptake through CD44, improves pharmacokinetics, tumor localization, and anticancer efficacy while reducing systemic toxicity. This review provides a comprehensive overview of HA-based NPs, highlighting their potential to address limitations in cancer treatment and inspire further innovation. The targeting efficiency of HA-based NPs can be further optimized by integrating passive (e.g., PEGylation), active (e.g., ligand conjugation), and stimuli-responsive mechanisms (e.g., pH, redox, light, enzyme activity, and temperature sensitivity). These NPs also enable therapeutic combinations, such as co-delivery of chemotherapeutics with gene therapies (e.g., siRNA) and integration of photothermal and photodynamic therapies, alongside immune checkpoint inhibitors, amplifying therapeutic synergy. Despite promising preclinical results, challenges such as scalability, stability, long-term safety, ethical and regulatory hurdles, and high costs persist. Nonetheless, HA-based NPs represent a cutting-edge approach, combining biocompatibility, precision targeting, and multimodal functionality to combat cancer effectively, while mitigating side effects.
Collapse
Affiliation(s)
- Alaa Raad Al Jayoush
- Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Mohamed Haider
- Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates
| | - Saeed Ahmad Khan
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates; Department of Pharmacy, Kohat University of Science and Technology, Kohat 26000, Pakistan
| | - Zahid Hussain
- Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah 27272, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates.
| |
Collapse
|
14
|
Lee CE, Noh KM, Kim S, Hong J, Kim K. Recent Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Engineering Strategies for Precise Strike Therapy against Tumor. Biomater Res 2025; 29:0170. [PMID: 40110051 PMCID: PMC11922527 DOI: 10.34133/bmr.0170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 02/23/2025] [Accepted: 03/02/2025] [Indexed: 03/22/2025] Open
Abstract
Effective drug delivery relies on the selection of suitable carriers, which is crucial for protein-based therapeutics such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). One of the key advantages of TRAIL is its ability to selectively induce apoptosis in cancer cells excluding healthy tissues by binding to death receptors DR4 and DR5, which are highly expressed in various cancer cells. Despite this promise, the clinical application of TRAIL has been limited by its short half-life, limited stability, and inefficient delivery to tumor sites. To overcome currently available clinical and engineering approaches, a series of sophisticated strategies is required: (a) the design of biomaterial-mediated carriers for enhanced targeting efficacy, particularly via optimizing selected materials, composition, formulation, and surface modulation. Moreover, (b) development of genetically modified cellular products for augmented TRAIL secretion toward tumor microenvironments and (c) cell surface engineering techniques for TRAIL immobilization onto infusible cell populations are also discussed in the present review. Among these approaches, living cell-based carriers offer the distinct advantage of systemically administered TRAIL-functionalized cells capturing circulating tumor cells in the bloodstream, thereby preventing secondary tumor formation. This review provides insight into the development of novel TRAIL delivery platforms, discusses considerations for clinical translation, and suggests future directions and complementary strategies to advance the field of TRAIL-based cancer therapeutics.
Collapse
Affiliation(s)
- Chae Eun Lee
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul 04620, Republic of Korea
| | - Kyung Mu Noh
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul 04620, Republic of Korea
| | - Sungjun Kim
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul 04620, Republic of Korea
| | - Jiyeon Hong
- School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea
| | - Kyobum Kim
- Department of Chemical and Biochemical Engineering, Dongguk University, Seoul 04620, Republic of Korea
| |
Collapse
|
15
|
Shaikh S, Chary PS, Mehra NK. Tyrosine Kinase Inhibitor Lenvatinib Based Nano Formulations and Cutting-Edge Scale-Up Technologies in revolutionizing Cancer Therapy. ACS APPLIED BIO MATERIALS 2025; 8:1749-1784. [PMID: 40091597 DOI: 10.1021/acsabm.4c01527] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/19/2025]
Abstract
Lenvatinib (LEN), a tyrosine kinase inhibitor, has emerged as a promising therapeutic agent for various solid tumors. Nevertheless, a number of constraints, including diminished bioavailability, incapacity to elicit localized inflammation, and inability to selectively accumulate at the tumor site, may impede the comprehensive exploitation of its versatile tyrosine kinase inhibitory capabilities. In order to achieve targeted delivery of LEN while also reducing its high dose used in conventional therapeutics, nanoformulation approaches can be adopted. The integration of LEN into various nanoformulations, such as nanoparticles, nanocrystals, high density lipoproteins (HDLs), liposomes, and micelles, is discussed, highlighting the advantages of these innovative approaches in a comparative manner; however, given that the current methods of nanoformulation synthesis employ toxic organic solvents and chemicals, there is an imperative need for exploring alternative, environmentally friendly approaches. The multifaceted effects of nanocarriers have rendered them profoundly applicable within the biomedical domain, serving as instrumental entities in various capacities such as vehicles for drug delivery and genetic material, diagnostic agents, facilitators of photothermal therapy, and radiotherapy. However, the scalability of these nanotechnological methodologies must be rigorously investigated and addressed to refine drug delivery mechanisms. This endeavor offers promising prospects for revolutionizing strategies in cancer therapeutics, thereby laying the foundation for future research in scale-up techniques in the pursuit of more effective and less toxic therapies for cancer.
Collapse
Affiliation(s)
- Samia Shaikh
- Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana 500029, India
| | - Padakanti Sandeep Chary
- Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana 500029, India
| | - Neelesh Kumar Mehra
- Pharmaceutical Nanotechnology Research Laboratory, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Hyderabad, Telangana 500029, India
| |
Collapse
|
16
|
Srivastav AK, Jaiswal J, Rajput PK, Yadav UCS, Singh R, Kumar U. In silico and in vitro profiling of sphingomyelin loaded zein nanoconstructs with optimized aromatic interactions and pharmacokinetics for colon cancer therapeutics. Int J Biol Macromol 2025; 307:141845. [PMID: 40057096 DOI: 10.1016/j.ijbiomac.2025.141845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 02/25/2025] [Accepted: 03/05/2025] [Indexed: 03/15/2025]
Abstract
To enhance therapeutic efficacy and achieve controlled drug release for colon cancer therapeutics, this study focuses on developing a hydrocolloid-based, pH-responsive biocompatible nanocarrier. We synthesized sphingomyelin (SM)-loaded zein nanoparticles (SM-LNPs) stabilized using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC), leveraging the aromatic interactions of zein to optimize drug encapsulation and release kinetics. In silico molecular docking and molecular dynamics (MD) simulations demonstrated strong intermolecular interactions between zein, SM, and EDC, supporting the formulation's rational design. Comprehensive physicochemical characterization confirmed the stability and structural integrity of SM-LNPs. Dynamic light scattering (DLS) and field emission scanning electron microscopy (FE-SEM) analyses revealed a monodispersed, spherical morphology with an optimized particle size suitable for oral drug delivery. In vitro drug release studies indicated a sustained and pH-responsive release profile, with 90.60 % of SM released at pH 6.8, mimicking intestinal conditions. Cell viability assays using HCT 116 colon cancer cells showed that SM-LNPs exhibited significantly enhanced cytotoxicity (41.44 % reduction in cell viability) compared to free SM, confirming their potential for cancer therapeutics. Additionally, pharmacokinetic simulations validated the controlled release and systemic retention of SM, supporting its suitability for oral administration. Our findings demonstrate that SM-LNPs offer a promising drug delivery platform with enhanced stability, pH response release, and improved bioactivity, paving the way for their potential application in colon cancer treatment. This research provides critical insights into nanocarrier design, drug delivery kinetics, and biomaterial-based therapeutic strategies for precision oncology.
Collapse
Affiliation(s)
- Amit Kumar Srivastav
- School of Nano Sciences, Central University of Gujarat, Gandhinagar, India; Department of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA, USA
| | - Jyoti Jaiswal
- School of Nano Sciences, Central University of Gujarat, Gandhinagar, India; Department of Microbiology & Biotechnology, Gujarat University, Ahmedabad, Gujarat, India
| | - Pradeep Kumar Rajput
- Special Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
| | - Umesh C S Yadav
- Special Center for Molecular Medicine, Jawaharlal Nehru University, New Delhi, India
| | - Rajesh Singh
- Department of Microbiology, Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA, USA; Cancer Health Equity Institute, Morehouse School of Medicine, Atlanta, GA, USA
| | - Umesh Kumar
- School of Nano Sciences, Central University of Gujarat, Gandhinagar, India; Nutrition Biology Department, School of Interdisciplinary and Applied Sciences, Central University of Haryana, Mahendergarh, Haryana, India.
| |
Collapse
|
17
|
Li Y, Liu P, Zhang B, Chen J, Yan Y. Global trends and research hotspots in nanodrug delivery systems for breast cancer therapy: a bibliometric analysis (2013-2023). Discov Oncol 2025; 16:269. [PMID: 40047951 PMCID: PMC11885776 DOI: 10.1007/s12672-025-02014-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 02/24/2025] [Indexed: 03/09/2025] Open
Abstract
OBJECTIVE Nanomedicine offers fresh approaches for breast cancer treatment, countering traditional limitations. The nanodrug delivery system's precision and biocompatibility hold promise, yet integration hurdles remain. This study reviews nano delivery systems in breast cancer therapy from 2013 to 2023, guiding future research directions. METHODS In this study, we conducted a comprehensive search on Web of Science database (Guilin Medical University purchase edition) and downloaded literature related to the field published between 2013 and 2023. We analyzed these publications using R software, VOSviewer, and CiteSpace software. RESULTS This study reviewed 2632 documents, showing a steady publication increase from 2013 to 2023, peaking at 408 in 2022. China, USA, India, and Iran were prominent in publishing. The Chinese Academy of Sciences and Tabriz University of Medical Science were key collaboration centers. Notably, the Journal of Controlled Release and Biomaterials ranked among the top 10 journals for publications and citations, establishing their field representation. Key terms like "breast cancer," "nanoparticles," "drug delivery," "in-vitro," and "delivery" were widely used. Research focused on optimizing drug targeting, utilizing the tumor microenvironment for drug delivery, and improving delivery efficiency. CONCLUSION The nanodrug delivery system, as an innovative drug delivery approach, offers numerous advantages and has garnered global attention from researchers. This study provides an analysis of the status and hotspots in nano delivery systems within the realm of breast cancer therapy, offering valuable insights for future research in this domain.
Collapse
Affiliation(s)
- Yang Li
- Department of Pharmacy, The First People's Hospital of Yulin, Yulin, Guangxi, China
| | - Pingping Liu
- Sanya Central Hospital (The Third People's Hospital of Hainan Province), Hainan, China
| | - Bo Zhang
- Scientific Research Center, Guilin Medical University, Guilin, China
| | - Juan Chen
- Sanya Central Hospital (The Third People's Hospital of Hainan Province), Hainan, China
| | - Yuanyuan Yan
- Sanya Central Hospital (The Third People's Hospital of Hainan Province), Hainan, China.
| |
Collapse
|
18
|
Zhang L, Wang Y, Li Y, Chen ZS, Hu C. Advanced materials for cancer treatment and beyond. Front Pharmacol 2025; 16:1557155. [PMID: 40110134 PMCID: PMC11920709 DOI: 10.3389/fphar.2025.1557155] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Accepted: 02/13/2025] [Indexed: 03/22/2025] Open
Abstract
Conservative anti-cancer treatment represented by chemotherapy and surgery lacks tumor-specificity and could hardly resolve the problems associated with multidrug resistance (MDR) in cancers. Novel therapeutic materials in cancer treatment, such as those with anti-MDR or controllable treatment features, represent a significant trend due to their advantages of high and specific efficacy and timely intervention of cancer progress. In addition to their excellent biocompatibility and specificity, they can be utilized in therapies that require ease of operation, provided they are designed with high detection sensitivity. In this review, we summarize a series of recently developed materials that exhibit these advantages, including immune-enhancing and tumor microenvironment (TME)- responsive materials, and those with integrated therapeutic and imaging capabilities. We also introduce advanced modification approaches that can impart essential targeting functionalities to these materials.
Collapse
Affiliation(s)
- Lei Zhang
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
- College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China
- State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, China
| | - Yanan Wang
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China
- College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Yangjia Li
- National Engineering Research Center for Sugarcane, Fujian Agriculture and Forestry University, Fuzhou, China
| | - Zhe-Sheng Chen
- Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, United States
| | - Chaohua Hu
- National Engineering Research Center for Sugarcane, Fujian Agriculture and Forestry University, Fuzhou, China
| |
Collapse
|
19
|
Panja P, Manne U, Awasthi V, Bhattacharya R, Mukherjee P. Interrogation of the tumor microenvironment by nanoparticles. Cancer Lett 2025; 612:217454. [PMID: 39805387 DOI: 10.1016/j.canlet.2025.217454] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 01/08/2025] [Accepted: 01/10/2025] [Indexed: 01/16/2025]
Abstract
The tumor microenvironment (TME) plays a pivotal role in cancer progression by fostering intricate multicellular crosstalk among cancer cells, stromal cells, and immune cells. This review explores the emerging paradigm of utilizing nanoparticles to disrupt this crosstalk within the TME as a therapeutic strategy. Nanoparticles are engineered with precise physicochemical properties to target specific cell types and deliver therapeutic payloads, thereby inhibiting critical signaling pathways involved in tumor growth, invasion, and metastasis. The mechanisms involved include modulation of the immune response, interference with growth factor signaling, and induction of programmed cell death in cancer cells. Challenges such as biocompatibility, efficient delivery, and potential development of resistance are discussed alongside promising advancements in nanoparticle design. Moving forward, integration of nanoparticle-based therapies with existing treatment modalities holds great potential for enhancing therapeutic efficacy and personalized medicine in cancer therapy.
Collapse
Affiliation(s)
- Prasanta Panja
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
| | - Upender Manne
- Department of Pathology, University of Alabama at Birmingham, Birmingham, AL, USA; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Vibhudutta Awasthi
- Department of Pharmaceutical Sciences, University of Oklahoma Health Science Center, Suite 309, 1110 N. Stonewall Avenue, Oklahoma City, OK, 73117, USA
| | - Resham Bhattacharya
- Department of Obstetrics and Gynecology, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA
| | - Priyabrata Mukherjee
- Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA; Peggy and Charles Stephenson Cancer Center, The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, USA.
| |
Collapse
|
20
|
Kim K. Hybrid Systems of Gels and Nanoparticles for Cancer Therapy: Advances in Multifunctional Therapeutic Platforms. Gels 2025; 11:170. [PMID: 40136875 PMCID: PMC11941994 DOI: 10.3390/gels11030170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 02/23/2025] [Accepted: 02/25/2025] [Indexed: 03/27/2025] Open
Abstract
Cancer is a global health concern. Various therapeutic approaches, including chemotherapy, photodynamic therapy, and immunotherapy, have been developed for cancer treatment. Silica nanoparticles, quantum dots, and metal-organic framework (MOF)-based nanomedicines have gained interest in cancer therapy because of their selective accumulation in tumors via the enhanced permeability and retention (EPR) effect. However, bare nanoparticles face challenges including poor biocompatibility, low stability, limited drug-loading capacity, and rapid clearance by the reticuloendothelial system (RES). Gels with unique three-dimensional network structures formed through various interactions such as covalent and hydrogen bonds are emerging as promising materials for addressing these challenges. Gel hybridization enhances biocompatibility, facilitates controlled drug release, and confers cancer-targeting abilities to nanoparticles. This review discusses gel-nanoparticle hybrid systems for cancer treatment developed in the past five years and analyzes the roles of gels in these systems.
Collapse
Affiliation(s)
- Kibeom Kim
- Department of Chemistry and Life Science, Sahmyook University, Seoul 01795, Republic of Korea
| |
Collapse
|
21
|
Du S, Wu K, Guan Y, Lin X, Gao S, Huang S, Shi X, Wang L, Chen X, Chen T. Biomimetic celastrol nanocrystals with enhanced efficacy and reduced toxicity for suppressing breast cancer invasion and metastasis. Int J Pharm 2025; 671:125221. [PMID: 39832573 DOI: 10.1016/j.ijpharm.2025.125221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 12/30/2024] [Accepted: 01/12/2025] [Indexed: 01/22/2025]
Abstract
Breast cancer and its lung metastases pose significant threats to women's health worldwide, impacting their quality of life. Although several therapeutic strategies against breast cancer have been developed, they often cause serious side effects due to their high toxicity and low specificity. Therefore, novel therapeutic strategies that offer potent anti-tumor activity with minimal toxicity are urgently needed to combat the threat of breast cancer and lung metastases. Celastrol (Cela), a triterpenoid extracted from Tripterygium wilfordii, exerts anti-tumor effects by inhibiting tumor angiogenesis as well as tumor cell proliferation, invasion, and metastasis. However, its poor solubility and potential for severe organ toxicity hinder its clinical application. Therefore, in this study, we prepared Cela nanocrystals (Cela-NCs), which effectively increased the solubility of Cela and improved its bioavailability. Subsequently, Cela-NCs were encapsulated within the cell membrane (CCM) derived from breast cancer cells to generate CCM/Cela-NCs and leverage the homologous targeting ability of the CCM. Notably, CCM/Cela-NCs showed immune evasion and could homologously target tumor cells. Both in vitro and in vivo, CCM/Cela-NCs could effectively inhibit the growth and metastasis of breast cancer cells. They also exerted minimal hepatotoxicity in mice during treatment. In conclusion, this Cela-based biomimetic strategy that exploits the biological properties of tumor cells offers a new idea for the effective treatment of breast cancer and its lung metastasis.
Collapse
Affiliation(s)
- Shuang Du
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405 China
| | - Kemeng Wu
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405 China
| | - Yucheng Guan
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405 China
| | - Xiangping Lin
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405 China
| | - Sijia Gao
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078 China
| | - Shuiqing Huang
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405 China
| | - Xuguang Shi
- College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 51006 China
| | - Lisheng Wang
- College of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 51006 China.
| | - Xiaojia Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau 999078 China.
| | - Tongkai Chen
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405 China.
| |
Collapse
|
22
|
Yang M, Wang X, Peng M, Wang F, Hou S, Xing R, Chen A. Nanomaterials Enhanced Sonodynamic Therapy for Multiple Tumor Treatment. NANO-MICRO LETTERS 2025; 17:157. [PMID: 39992547 PMCID: PMC11850698 DOI: 10.1007/s40820-025-01666-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Accepted: 01/08/2025] [Indexed: 02/25/2025]
Abstract
Sonodynamic therapy (SDT) as an emerging modality for malignant tumors mainly involves in sonosensitizers and low-intensity ultrasound (US), which can safely penetrate the tissue without significant attenuation. SDT not only has the advantages including high precision, non-invasiveness, and minimal side effects, but also overcomes the limitation of low penetration of light to deep tumors. The cytotoxic reactive oxygen species can be produced by the utilization of sonosensitizers combined with US and kill tumor cells. However, the underlying mechanism of SDT has not been elucidated, and its unsatisfactory efficiency retards its further clinical application. Herein, we shed light on the main mechanisms of SDT and the types of sonosensitizers, including organic sonosensitizers and inorganic sonosensitizers. Due to the development of nanotechnology, many novel nanoplatforms are utilized in this arisen field to solve the barriers of sonosensitizers and enable continuous innovation. This review also highlights the potential advantages of nanosonosensitizers and focus on the enhanced efficiency of SDT based on nanosonosensitizers with monotherapy or synergistic therapy for deep tumors that are difficult to reach by traditional treatment, especially orthotopic cancers.
Collapse
Affiliation(s)
- Mengyao Yang
- College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, 050018, People's Republic of China
| | - Xin Wang
- College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, 050018, People's Republic of China
| | - Mengke Peng
- College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, 050018, People's Republic of China
| | - Fei Wang
- College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, 050018, People's Republic of China
| | - Senlin Hou
- The Second Hospital of Hebei Medical University, Shijiazhuang, 050000, People's Republic of China.
| | - Ruirui Xing
- State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 100190, People's Republic of China.
| | - Aibing Chen
- College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, 050018, People's Republic of China.
| |
Collapse
|
23
|
Moni SS, Moshi JM, Matou-Nasri S, Alotaibi S, Hawsawi YM, Elmobark ME, Hakami AMS, Jeraiby MA, Sulayli AA, Moafa HN. Advances in Materials Science for Precision Melanoma Therapy: Nanotechnology-Enhanced Drug Delivery Systems. Pharmaceutics 2025; 17:296. [PMID: 40142960 PMCID: PMC11945159 DOI: 10.3390/pharmaceutics17030296] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 02/14/2025] [Accepted: 02/19/2025] [Indexed: 03/28/2025] Open
Abstract
Melanoma, a highly aggressive form of skin cancer, poses a major therapeutic challenge due to its metastatic potential, resistance to conventional therapies, and the complexity of the tumor microenvironment (TME). Materials science and nanotechnology advances have led to using nanocarriers such as liposomes, dendrimers, polymeric nanoparticles, and metallic nanoparticles as transformative solutions for precision melanoma therapy. This review summarizes findings from Web of Science, PubMed, EMBASE, Scopus, and Google Scholar and highlights the role of nanotechnology in overcoming melanoma treatment barriers. Nanoparticles facilitate passive and active targeting through mechanisms such as the enhanced permeability and retention (EPR) effect and functionalization with tumor-specific ligands, thereby improving the accuracy of drug delivery and reducing systemic toxicity. Stimuli-responsive systems and multi-stage targeting further improve therapeutic precision and overcome challenges such as poor tumor penetration and drug resistance. Emerging therapeutic platforms combine diagnostic imaging with therapeutic delivery, paving the way for personalized medicine. However, there are still issues with scalability, biocompatibility, and regulatory compliance. This comprehensive review highlights the potential of integrating nanotechnology with advances in genetics and proteomics, scalable, and patient-specific therapies. These interdisciplinary innovations promise to redefine the treatment of melanoma and provide safer, more effective, and more accessible treatments. Continued research is essential to bridge the gap between evidence-based scientific advances and clinical applications.
Collapse
Affiliation(s)
- Sivakumar S. Moni
- College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia;
- Health Research Centre, Jazan University, Jazan 45142, Saudi Arabia
| | - Jobran M. Moshi
- Department of Medical Laboratory Technology, College of Nursing and Health Science, Jazan University, Jazan 45142, Saudi Arabia
- Health Research Centre, Jazan University, Jazan 45142, Saudi Arabia
| | - Sabine Matou-Nasri
- Blood and Cancer Research Department, King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Ministry of National Guard-Health Affairs, Riyadh 11481, Saudi Arabia;
- Biosciences Department, Faculty of the School for Systems Biology, George Mason University, Manassas, VA 22030, USA
| | - Shmoukh Alotaibi
- Research Center, King Faisal Specialist Hospital and Research Center, Jeddah 23433, Saudi Arabia; (S.A.); (Y.M.H.)
| | - Yousef M. Hawsawi
- Research Center, King Faisal Specialist Hospital and Research Center, Jeddah 23433, Saudi Arabia; (S.A.); (Y.M.H.)
- Department of Biochemistry and Molecular Medicine, College of Medicine, Al-Faisal University, Riyadh 11533, Saudi Arabia
| | | | | | - Mohammed A. Jeraiby
- Department of Basic Medical Science, Faculty of Medicine, Jazan University, Jazan 45142, Saudi Arabia;
| | - Ahmed A. Sulayli
- Laboratory Department, Prince Mohammed bin Nasser Hospital, Jazan Health Cluster, Jazan 82734, Saudi Arabia;
| | - Hassan N. Moafa
- Department of Public Health, College of Nursing and Health Sciences, Jazan University, Jazan 45142, Saudi Arabia;
- Department of Quality and Patients Safety, Jazan University Hospital, Jazan University, Jazan 45142, Saudi Arabia
| |
Collapse
|
24
|
Lim JX, Yong YK, Dewi FRP, Chan SY, Lim V. Nanoscale strategies: doxorubicin resistance challenges and enhancing cancer therapy with advanced nanotechnological approaches. Drug Deliv Transl Res 2025:10.1007/s13346-025-01790-3. [PMID: 39955406 DOI: 10.1007/s13346-025-01790-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/07/2025] [Indexed: 02/17/2025]
Abstract
Doxorubicin (DOX), an anthracycline, is widely used in cancer treatment by interfering RNA and DNA synthesis. Its broad antitumour spectrum makes it an effective therapy for a wide array of cancers. However, the prevailing drug-resistant cancer has proven to be a significant drawback to the success of the conventional chemotherapy regime and DOX has been identified as a major hurdle. Furthermore, the clinical application of DOX has been limited by rapid breakdown, increased toxicity, and decreased half-time life, highlighting an urgent need for more innovative delivery methods. Although advancements have been made, achieving a complete cure for cancer remains elusive. The development of nanoparticles offers a promising avenue for the precise delivery of DOX into the tumour microenvironment, aiming to increase the drug concentration at the target site while reducing side effects. Despite the good aspects of this technology, the classical nanoparticles struggle with issues such as premature drug leakage, low bioavailability, and insufficient penetration into tumours due to an inadequate enhanced permeability and retention (EPR) effect. Recent advancements have focused on creating stimuli-responsive nanoparticles and employing various chemosensitisers, including natural compounds and nucleic acids, fortifying the efficacy of DOX against resistant cancers. The efforts to refine nanoparticle targeting precision to improve DOX delivery are reviewed. This includes using receptor-mediated endocytosis systems to maximise the internalisation of drugs. The potential benefits and drawbacks of these novel techniques constitute significant areas of ongoing study, pointing to a promising path forward in addressing the challenges posed by drug-resistant cancers.
Collapse
Affiliation(s)
- Jian Xin Lim
- Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam 13200 Kepala Batas, Penang, Malaysia
| | - Yoke Keong Yong
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Selangor, Malaysia
| | - Firli Rahmah Primula Dewi
- Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya, 60115, Indonesia
| | - Siok Yee Chan
- School of Pharmaceutical Sciences, Universiti Sains Malaysia, 11800, Minden, Pulau Pinang, Malaysia
| | - Vuanghao Lim
- Advanced Medical and Dental Institute, Universiti Sains Malaysia, Bertam 13200 Kepala Batas, Penang, Malaysia.
| |
Collapse
|
25
|
Martin-Aubert S, Avrillon K, Tournier N, Bordat A, Tran VL, Ibrahim N, Kereselidze D, Jego B, Potiron L, Tsapis N, Nicolas J, Boissenot T, Truillet C. Successful repositioning of mertansine for improved chemotherapy by combining a polymer prodrug approach and PET imaging. J Control Release 2025; 378:803-813. [PMID: 39719212 DOI: 10.1016/j.jconrel.2024.12.050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2024] [Revised: 12/01/2024] [Accepted: 12/19/2024] [Indexed: 12/26/2024]
Abstract
Mertansine (DM1), a potent tumor-killing maytansinoid, requires conjugation to antibodies or incorporation into nanocarriers due to its high toxicity. However, these carriers often result in undesirable biodistribution, leading to rapid and long-term accumulation in the kidneys or liver and potentially increased toxicity. To overcome this limitation, we used the hydrophilic, biocompatible, and stealth properties of polyacrylamide (PAAm) as a scaffold to develop water-soluble PAAm-DM1 polymer prodrugs, leveraging PAAm's previous success in delivering paclitaxel via subcutaneous administration. To monitor distribution and predict efficacy, we have imparted Positron Emission Tomography (PET) imaging capabilities to well-defined PAAm-DM1 polymer prodrugs. Our studies demonstrated the same tumor accumulation and the same distribution of PAAm-DM1 in the main organs such as liver, kidneys muscle, regardless of delivery route (subcutaneous or intravenous). Interestingly, tumor accumulation of PAAm-DM1 was primarily driven by passive accumulation, as indicated by PET imaging, without significantly altering treatment efficacy. This suggests complex mechanisms, possibly involving immune system interactions by influencing notably the metabolism and clearance. To enhance therapeutic outcomes, we combined the polymer prodrug with immunotherapy, specifically anti-CTLA4. Our findings highlight the promising potential of PAAm-DM1, offering a novel formulation strategy for DM1 in cancer therapy.
Collapse
Affiliation(s)
- Soizic Martin-Aubert
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, SHFJ, Orsay 91401, France..
| | - Kevin Avrillon
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, SHFJ, Orsay 91401, France
| | - Nicolas Tournier
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, SHFJ, Orsay 91401, France..
| | | | - Vu Long Tran
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, SHFJ, Orsay 91401, France
| | - Nada Ibrahim
- Imescia, Université Paris-Saclay, 91400 Saclay, France
| | - Dimitri Kereselidze
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, SHFJ, Orsay 91401, France
| | - Benoit Jego
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, SHFJ, Orsay 91401, France..
| | - Léa Potiron
- Imescia, Université Paris-Saclay, 91400 Saclay, France
| | - Nicolas Tsapis
- Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, 91400 Orsay, France.
| | - Julien Nicolas
- Université Paris-Saclay, CNRS, Institut Galien Paris-Saclay, 91400 Orsay, France.
| | | | - Charles Truillet
- Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, SHFJ, Orsay 91401, France..
| |
Collapse
|
26
|
Takeshita K, Nakagawa Y, Yokoyama E, Shinohara N, Miura K, Naka S, Nishida M, Yasukawa K, Ohta Y, Fang J, Okazaki S. Comparison of the accumulation manner of a macromolecular drug between two mouse tumour models: study with magnetic resonance imaging and the model macromolecular drug, gadolinium-conjugated dextran. J Drug Target 2025; 33:268-280. [PMID: 39325650 DOI: 10.1080/1061186x.2024.2409886] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 08/27/2024] [Accepted: 09/21/2024] [Indexed: 09/28/2024]
Abstract
A knowledge of the difference of spatio-temporal behaviour of nanomedicine in different type of tumour models is important to develop well-targeted nanomedicine for tumour. In this study, intratumoral accumulation of the model nanomedicine, gadolinium-conjugated dextran (Gd-Dex), was examined with magnetic resonance imaging in two tumour models; mouse sarcoma S180 and radiation-induced mouse fibrosarcoma RIF-1. From time-course of the distribution images, the plasma-to-tumour interstitial tissue transfer constant (Ktrans) and fractional plasma volume (Vp) were calculated and mapped. Gd-Dex preferentially distributed to the marginal region of S180 tumours immediately after its injection, and then started to accumulate in some parts of the central region. Ktrans and Vp values were large in the marginal region, while only Ktrans was large in some parts of the central region. In contrast, the distribution of Gd-Dex in RIF-1 tumours was fairly homogeneous, and may have resulted from the homogeneous distributions of Ktrans and Vp. The amounts of Gd-Dex that accumulated in entire tumours in both tumour models correlated with the volume of tumours; however, accumulation in large S180 tumours deviated from the correlation in the early phase. The differences in the manner and pharmacokinetics of nanomedicine among tumour models may affect the accumulation of the medicine.
Collapse
Affiliation(s)
- Keizo Takeshita
- Laboratory of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
| | - Yohei Nakagawa
- Laboratory of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
| | - Eika Yokoyama
- Laboratory of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
| | - Nana Shinohara
- Laboratory of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
| | - Kayoko Miura
- Laboratory of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
| | - Shiho Naka
- Laboratory of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
| | - Masashi Nishida
- Department of Nanoscience, Faculty of Engineering, Sojo University, Kumamoto, Japan
| | - Keiji Yasukawa
- Laboratory of Advanced Pharmacology, Faculty of Pharmaceutical Sciences, Daiichi University of Pharmacy, Fukuoka, Japan
- Biostatistics Center, Kurume University, Kurume, Fukuoka, Japan
| | - Yuhei Ohta
- Laboratory of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
| | - Jun Fang
- Laboratory of Microbiology and Oncology, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
| | - Shoko Okazaki
- Laboratory of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Sojo University, Kumamoto, Japan
| |
Collapse
|
27
|
Chen Y, Liu L, Li M, Chen X, Li Y, Tao J, Deng Y. Nanoparticle-enabled In Situ drug potency activation for enhanced tumor-specific therapy. Eur J Pharm Sci 2025; 205:106989. [PMID: 39675436 DOI: 10.1016/j.ejps.2024.106989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2024] [Revised: 12/08/2024] [Accepted: 12/10/2024] [Indexed: 12/17/2024]
Abstract
Cancer treatment faces significant challenges including inadequate tumor specificity, drug resistance, and severe side effects, often resulting in unsatisfactory patient outcomes. Nanomedicines offer a transformative platform for tumor-targeted drug delivery and antitumor potency activation, providing an indispensable strategy for overcoming the severe damage to normal tissues caused by the inherent "always-on" cytotoxicity of conventional therapeutic agents. This review focuses on the emerging concept of "nanoparticle-enabled in situ drug potency activation", where inactive or minimally toxic agents are selectively activated within tumors to enhance the therapeutic efficacy and minimize the adverse effects. We systematically analyzed literature from PubMed and Web of Science databases spanning the last two decades, emphasizing experimental evidence supporting this in situ drug potency activation concept. Key strategies including stimuli-responsive prodrug nanoparticles, metal-induced activation, and bioorthogonal reactions are critically evaluated for their potential to overcome limitations in current cancer therapies. The findings highlight the potential of in situ potency activation as a promising alternative to conventional therapeutics, with far-reaching implications for advancing effective and safe cancer treatments.
Collapse
Affiliation(s)
- Yitian Chen
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Lishan Liu
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Ming Li
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Xiaolian Chen
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China
| | - Yaoqi Li
- Department of Pharmacy, the First Affiliated Hospital of Soochow University, Suzhou 215006, China
| | - Jing Tao
- Department of Pharmacy, the First Affiliated Hospital of Soochow University, Suzhou 215006, China.
| | - Yibin Deng
- Jiangsu Key Laboratory of Neuropsychiatric Diseases, and College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, China; Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development, Soochow University, Suzhou 215123, China; State Key Laboratory of Molecular Engineering of Polymers, Fudan University, Shanghai 200438, China.
| |
Collapse
|
28
|
Jain A, Mishra AK, Hurkat P, Shilpi S, Mody N, Jain SK. Navigating liver cancer: Precision targeting for enhanced treatment outcomes. Drug Deliv Transl Res 2025:10.1007/s13346-024-01780-x. [PMID: 39847205 DOI: 10.1007/s13346-024-01780-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/18/2024] [Indexed: 01/24/2025]
Abstract
Cancer treatments such as surgery and chemotherapy have several limitations, including ineffectiveness against large or persistent tumors, high relapse rates, drug toxicity, and non-specificity of therapy. Researchers are exploring advanced strategies for treating this life-threatening disease to address these challenges. One promising approach is targeted drug delivery using prodrugs or surface modification with receptor-specific moieties for active or passive targeting. While various drug delivery systems have shown potential for reaching hepatic cells, nano-carriers offer significant size, distribution, and targetability advantages. Engineered nanocarriers can be customized to achieve effective and safe targeting of tumors by manipulating physical characteristics such as particle size or attaching receptor-specific ligands. This method is particularly advantageous in treating liver cancer by targeting specific hepatocyte receptors and enzymatic pathways for both passive and active therapeutic strategies. It highlights the epidemiology of liver cancer and provides an in-depth analysis of the various targeting approaches, including prodrugs, liposomes, magneto-liposomes, micelles, glycol-dendrimers, magnetic nanoparticles, chylomicron-based emulsion, and quantum dots surface modification with receptor-specific moieties. The insights from this review can be immensely significant for preclinical and clinical researchers working towards developing effective treatments for liver cancer. By utilizing these novel strategies, we can overcome the limitations of conventional therapies and offer better outcomes for liver cancer patients.
Collapse
Affiliation(s)
- Ankit Jain
- Department of Pharmacy, Birla Institute of Technology and Science (BITS), Pilani Campus, Pilani, Rajasthan, 333031, India.
| | - Ashwini Kumar Mishra
- Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM'S NMIMS Deemed-to-be University, Shirpur, Maharashtra, 425405, India
- Central Ayurveda Research Institute, Jhansi, Uttar Pradesh, 284003, India
| | - Pooja Hurkat
- Dr. Hari Singh Gour Central University, Sagar, 470003, MP, India
| | - Satish Shilpi
- School of Pharmaceuticals and Population Health Informatics, FOP, DIT University, Dehradun, Uttarakahnad, India
| | - Nishi Mody
- Dr. Hari Singh Gour Central University, Sagar, 470003, MP, India
| | | |
Collapse
|
29
|
Basingab FS, Alshahrani OA, Alansari IH, Almarghalani NA, Alshelali NH, Alsaiary AH, Alharbi N, Zaher KA. From Pioneering Discoveries to Innovative Therapies: A Journey Through the History and Advancements of Nanoparticles in Breast Cancer Treatment. BREAST CANCER (DOVE MEDICAL PRESS) 2025; 17:27-51. [PMID: 39867813 PMCID: PMC11761866 DOI: 10.2147/bctt.s501448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Accepted: 01/03/2025] [Indexed: 01/28/2025]
Abstract
Nanoparticle technology has revolutionized breast cancer treatment by offering innovative solutions addressing the gaps in traditional treatment methods. This paper aimed to comprehensively explore the historical journey and advancements of nanoparticles in breast cancer treatment, highlighting their transformative impact on modern medicine. The discussion traces the evolution of nanoparticle-based therapies from their early conceptualization to their current applications and future potential. We initially explored the historical context of breast cancer treatment, highlighting the limitations of conventional therapies, such as surgery, radiation, and chemotherapy. The advent of nanotechnology has introduced a new era characterized by the development of various nanoparticles, including liposomes, dendrimers, and gold nanoparticles, designed to target cancer cells with remarkable precision. We further described the mechanisms of action for nanoparticles, including passive and active targeting, and reviewed significant breakthroughs and clinical trials that have validated their efficacy. Current applications of nanoparticles in breast cancer treatment have been examined, showcasing clinically approved therapies and comparing their effectiveness with traditional methods. This article also discusses the latest advancements in nanoparticle research, including drug delivery systems and combination therapy innovations, while addressing the current technical, biological, and regulatory challenges. The technical challenges include efficient and targeted delivery to tumor sites without affecting healthy tissue; biological, such as potential toxicity, immune system activation, or resistance mechanisms; economic, involving high production and scaling costs; and regulatory, requiring rigorous testing for safety, efficacy, and long-term effects to meet stringent approval standards. Finally, we have explored emerging trends, the potential for personalized medicine, and the ethical and social implications of this transformative technology. In conclusion, through comprehensive analysis and case studies, this paper underscores the profound impact of nanoparticles on breast cancer treatment and their future potential.
Collapse
Affiliation(s)
- Fatemah S Basingab
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, 21859, Saudi Arabia
- Immunology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21859, Saudi Arabia
| | - Omniah A Alshahrani
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, 21859, Saudi Arabia
| | - Ibtehal H Alansari
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, 21859, Saudi Arabia
| | - Nada A Almarghalani
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, 21859, Saudi Arabia
| | - Nada H Alshelali
- Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, 21859, Saudi Arabia
| | - Abeer Hamad Alsaiary
- Biology Department, College of Sciences, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Najwa Alharbi
- Department of Biology Science, Faculty of Science, King Abdulaziz University, Jeddah, 21859, Saudi Arabia
| | - Kawther A Zaher
- Immunology Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21859, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21859, Saudi Arabia
| |
Collapse
|
30
|
Kamal NH, Heikal LA, Abdallah OY. The future of cardiac repair: a review on cell-free nanotherapies for regenerative myocardial infarction. Drug Deliv Transl Res 2025:10.1007/s13346-024-01763-y. [PMID: 39833466 DOI: 10.1007/s13346-024-01763-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/06/2024] [Indexed: 01/22/2025]
Abstract
Cardiovascular diseases as myocardial infarction (MI) represent a major cause for morbidity and mortality worldwide. Even though, patients who survive MI are susceptible to high risk of heart failure. This is mainly attributed to the major loss of cardiomyocytes and limited regenerative potential of myocardium. Despite the availability of various cardiovascular drugs, they fail to address the main cause of MI. The optimum therapeutic goal should therefore focus on enhancing cardiac regeneration through cellular and cell-free therapeutic approaches. This review focused on different mechanisms of cardiac regeneration that can be achieved via non-cellular therapeutic modalities. Passive and active targeting of the infarcted myocardium using various nanoparticles that can be loaded with growth factors, drugs or affordable natural products can reduce negative ventricular remodeling, infarct size and the apoptotic rate of cardiomyocytes. In addition, injectable biomaterials-based nanocomposite can be used as a scaffold to support infarcted heart and recruit cells. Innovative affordable and less invasive cell-free approaches can be implemented to enhance cardiac regeneration post MI.
Collapse
Affiliation(s)
- Nermeen H Kamal
- Department of Pharmaceutics, Division of Pharmaceutical Sciences. College of Pharmacy, Arab Academy for Science, Technology and Maritime Transport, Alexandria, Egypt
| | - Lamia A Heikal
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 1 Khartoum Square, Azarita, P.O. Box 21521, Alexandria, Egypt.
| | - Ossama Y Abdallah
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, 1 Khartoum Square, Azarita, P.O. Box 21521, Alexandria, Egypt
| |
Collapse
|
31
|
Munyayi TA, Crous A. Advancing Cancer Drug Delivery with Nanoparticles: Challenges and Prospects in Mathematical Modeling for In Vivo and In Vitro Systems. Cancers (Basel) 2025; 17:198. [PMID: 39857980 PMCID: PMC11763932 DOI: 10.3390/cancers17020198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2024] [Revised: 12/30/2024] [Accepted: 01/07/2025] [Indexed: 01/27/2025] Open
Abstract
Mathematical models are crucial for predicting the behavior of drug conjugate nanoparticles and optimizing drug delivery systems in cancer therapy. These models simulate interactions among nanoparticle properties, tumor characteristics, and physiological conditions, including drug resistance and targeting specificity. However, they often rely on assumptions that may not accurately reflect in vivo conditions. In vitro studies, while useful, may not fully capture the complexities of the in vivo environment, leading to an overestimation of nanoparticle-based therapy effectiveness. Advancements in mathematical modeling, supported by preclinical data and artificial intelligence, are vital for refining nanoparticle-based therapies and improving their translation into effective clinical treatments.
Collapse
Affiliation(s)
| | - Anine Crous
- Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein 2028, South Africa
| |
Collapse
|
32
|
Dadashi H, Mashinchian M, Karimian-Shaddel A, Mohabbat A, Vandghanooni S, Eskandani M, Jahanban-Esfahlan R. Chitosan nanoparticles loaded with metformin and digoxin synergistically inhibit MCF-7 breast cancer cells through suppression of NOTCH-1 and HIF-1α gene expression. Int J Biol Macromol 2025; 287:138418. [PMID: 39645125 DOI: 10.1016/j.ijbiomac.2024.138418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2024] [Revised: 11/12/2024] [Accepted: 12/03/2024] [Indexed: 12/09/2024]
Abstract
This study investigated the potential anticancer efficacy of co-treating the MCF-7 breast cancer cell line with chitosan nanoparticles (Cs NPs) loaded with metformin (Met) and digoxin (Dig). The Cs NPs had a size range of 90.6-148.7 nm and a zeta potential of +11.7 to +11.9 mV, indicating a positive surface charge. Notably, the Cs NPs demonstrated high encapsulation efficiencies, with values of 90.97 ± 5.14 % for Met and 92.12 ± 3.81 % for Dig, indicating effective loading of both drugs. The results revealed that the co-delivery of Met and Dig via Cs NPs significantly enhanced the anticancer efficacy, outperforming the treatment with individual free drugs or their combination, thereby demonstrating the potential benefits of nanoparticle-mediated co-administration. The drugs-loaded Cs NPs induced a marked increase in apoptosis in MCF-7 cells, with a cell death rate of 67.56 %, and significantly reduced mammosphere size by 48.08 %, thereby demonstrating a superior therapeutic efficacy compared to treatment with individual free drugs or their combination. Notably, the drug-loaded Cs NPs exhibited potent anti-migratory and anti-angiogenic effects, significantly inhibiting cell migration and new blood vessel formation, which may contribute to overcoming the inherent resistance of tumors to conventional therapies. Mechanistically, the co-treatment with drugs-loaded Cs NPs was found to downregulate the expression of NOTCH-1 and HIF-1α, two key transcription factors involved in tumor cell survival and adaptation, suggesting that their inhibition is a crucial component of the therapeutic efficacy of this treatment strategy. Collectively, the findings of this study suggest that the co-delivery of Met and Dig via chitosan Cs NPs represents a promising therapeutic strategy for breast cancer, as it effectively targets key pathways involved in tumor growth and progression, and underscores the potential of Cs NPs as a versatile platform for cancer therapy.
Collapse
Affiliation(s)
- Hamed Dadashi
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Milad Mashinchian
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Alireza Karimian-Shaddel
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Aria Mohabbat
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Somayeh Vandghanooni
- Hematology and Oncology Research Center, Tabriz university of Medical Sciences, Tabriz, Iran
| | - Morteza Eskandani
- Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Rana Jahanban-Esfahlan
- Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
| |
Collapse
|
33
|
Oh S, Park SY, Seo HI, Chung I. L-Threonine-Derived Biodegradable Polyurethane Nanoparticles for Sustained Carboplatin Release. Pharmaceutics 2024; 17:28. [PMID: 39861677 PMCID: PMC11769003 DOI: 10.3390/pharmaceutics17010028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Revised: 12/20/2024] [Accepted: 12/26/2024] [Indexed: 01/27/2025] Open
Abstract
Background and objectives: The use of polymeric nanoparticles (NPs) in drug delivery systems offers the advantages of enhancing drug efficacy and minimizing side effects; Methods: In this study, L-threonine polyurethane (LTPU) NPs have been fabricated by water-in-oil-in-water emulsion and solvent evaporation using biodegradable and biocompatible LTPU. This polymer was pre-synthesized through the use of an amino acid-based chain extender, desaminotyrosyl L-threonine hexyl ester (DLTHE), where urethane bonds are formed by poly(lactic acid)-poly(ethylene glycol)-poly(lactic acid) (PLA-PEG-PLA) triblock copolymer and 1,6-hexamethylene diisocyanate (HDI). LTPU is designed to be degraded by hydrolysis and enzymatic activity due to the presence of ester bonds and peptide bonds within the polymer backbone. LTPU NPs were fabricated by water-in-oil-in-water double emulsion solvent evaporation methods; Results: The polymerization of LTPU was confirmed by 1H-NMR, 13C-NMR, and FT-IR spectroscopies. The molecular weights and polydispersity, determined with GPC, were 28,800 g/mol and 1.46, respectively. The morphology and size of NPs, characterized by DLS, FE-SEM, TEM, and confocal microscopy, showed smooth and spherical particles with diameters less than 200 nm; Conclusions: In addition, the drug loading, encapsulation efficiency, and drug release profiles, using UV-Vis spectroscopy, showed the highest encapsulation efficiency with 2.5% carboplatin and sustained release profile.
Collapse
Affiliation(s)
- Seoeun Oh
- Department of Polymer Science and Engineering, Pusan National University, Busan 46241, Republic of Korea
| | - Soo-Yong Park
- Department of Polymer Science and Engineering, Pusan National University, Busan 46241, Republic of Korea
| | - Hyung Il Seo
- Department of Surgery, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan 49241, Republic of Korea;
| | - Ildoo Chung
- Department of Polymer Science and Engineering, Pusan National University, Busan 46241, Republic of Korea
| |
Collapse
|
34
|
Liu D, Lu N, Zang F, Lu M, Zhang J, Zhao Y, Wan H, Wang M, Li QQ, Wang F, Luo S, Ma M, Shi F, Wu H, Tu J, Zhang Y. Magnetic Resonance Imaging-Based Radiogenomic Analysis Reveals Genomic Determinants for Nanoparticle Delivery into Tumors. ACS NANO 2024; 18:34615-34629. [PMID: 39663893 DOI: 10.1021/acsnano.4c09387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2024]
Abstract
Even though the enhanced permeability and retention (EPR) effect is applicable for the passive targeting of solid tumors, many nanodrugs have failed to achieve meaningful clinical outcomes due to the heterogeneity of EPR effect. Therefore, understanding the mechanism of the EPR effect is crucial to overcome the obstacles nanomedicines face in clinical translation. The aim of this study was to establish a reliable method to increase awareness of the critical influencing factors of nanoparticle (NP) transport into tumors based on the EPR effect using a combined radiogenomics and clinical magnetic resonance imaging (MRI) technique and gene set pathway enrichment analysis. Employing poly(lactic-co-glycolic acid) (PLGA)-coated Fe3O4 NPs as the contrast agent, the monolayer and multilayer distribution of the NPs were observed and quantitatively analyzed by MRI, improving the accuracy of evaluating vascular permeability by MRI. By performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of genes and pathways, we identified a variety of genes affecting vascular permeability, such as Cldn1, Dlg2, Bves, Prkag3, Cldn10, and Cldn8, which are related to tight junctions and control the permeability of blood vessels in tumors. The method presented here provides an MRI-supported approach to increase the breadth of data collected from genetic screens, reveals genetic evidence of the presence of NPs in tumors and lays a foundation for clinical patient stratification and personalized treatment.
Collapse
Affiliation(s)
- Di Liu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| | - Na Lu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| | - Fengchao Zang
- Jiangsu Key Laboratory of Molecular and Functional Imaging, School of Medicine, Southeast University, Nanjing 210096, P. R. China
| | - Mingze Lu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| | - Jingyue Zhang
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| | - Ying Zhao
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| | - Hao Wan
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| | - Mengjun Wang
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| | - Qian-Qian Li
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| | - Fei Wang
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| | - Shouhua Luo
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| | - Ming Ma
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| | - Fangfang Shi
- Department of Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210096, P. R. China
| | - Haoan Wu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| | - Jing Tu
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| | - Yu Zhang
- State Key Laboratory of Digital Medical Engineering, Jiangsu Key Laboratory for Biomaterials and Devices, School of Biological Science and Medical Engineering & Basic Medicine Research and Innovation Center of Ministry of Education, Zhongda Hospital, Southeast University, Nanjing 211102, P. R. China
| |
Collapse
|
35
|
Tiwari A, Tiwari V, Sharma A, Marrisetti AL, Kumar M, Rochani A, Kaushik D, Mittal V, Jyothi S R, Ali H, Hussain MS, Gupta G. Unlocking the potential: integrating phytoconstituents and nanotechnology in skin cancer therapy - A comprehensive review. JOURNAL OF COMPLEMENTARY & INTEGRATIVE MEDICINE 2024:jcim-2024-0338. [PMID: 39668578 DOI: 10.1515/jcim-2024-0338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 11/14/2024] [Indexed: 12/14/2024]
Abstract
Skin carcinoma, which includes basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma, is influenced by various factors such as genetic predisposition, chemical exposures, immune system imbalances, and ultraviolet (UV) radiation. This review delves into the mechanisms behind the development of these cancers, exploring the therapeutic potential of microbial, plant derived compounds and nanoparticles in advancing skin cancer treatments. Special attention is given to the cytotoxic effects of anti-neoplastic agents from microbial sources on different cancer cell lines, particularly melanoma. Additionally, the review highlights the role of phytochemicals - such as quercetin, resveratrol, and curcumin alongside vitamins, terpenoids, and sulforaphane, in management of skin cancers through mechanisms like apoptosis induction and cell cycle regulation. Recent advancements in nanotechnology-based drug delivery systems, including NP and microemulsion formulations, are also discussed for their enhanced ability to specifically target cancer cells. The diverse roles of NPs in skin cancer therapy, especially in terms of targeted drug delivery and immune modulation, are reviewed. These innovative NPs formulations have showed improved skin penetration and tumor-specific delivery, reduced systemic toxicity and enhanced therapeutic effectiveness.
Collapse
Affiliation(s)
- Abhishek Tiwari
- Department of Pharmaceutical Chemistry, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Lucknow Campus, Noida, Uttar Pradesh, India
- Amity University Uttar Pradesh, Sector 125, Noida 201313, Uttar Pradesh, India
| | - Varsha Tiwari
- Department of Pharmacognosy Chemistry, Amity Institute of Pharmacy, Lucknow Campus, Lucknow, India
- Amity University Uttar Pradesh, Sector 125, Noida 201313, Uttar Pradesh, India
| | - Ajay Sharma
- Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, New Delhi, India
| | - Arya Lakshmi Marrisetti
- Department of Pharmacognosy and Phytochemistry, School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, Pushp Vihar, New Delhi, India
| | - Manish Kumar
- Department of Pharmaceutics, ISF College of Pharmacy, Moga, Punjab, India
| | - Ankit Rochani
- Wegmans School of Pharmacy, St John Fisher University, Rochester, NY, USA
| | - Deepak Kaushik
- Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India
| | - Vineet Mittal
- Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India
| | - Renuka Jyothi S
- Department of Biotechnology and Genetics, Jain (Deemed-to-be) University, Bengaluru, Karnataka, India
| | - Haider Ali
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamil Nadu, India
- Department of Pharmacology, Kyrgyz State Medical College, Bishkek, Kyrgyzstan
| | - Md Sadique Hussain
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, Uttarakhand, India
| | - Gaurav Gupta
- Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, India
- Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman, UAE
| |
Collapse
|
36
|
Han CY, Choi SH, Chi SH, Hong JH, Cho YE, Kim J. Nano-fluorescence imaging: advancing lymphatic disease diagnosis and monitoring. NANO CONVERGENCE 2024; 11:53. [PMID: 39661218 PMCID: PMC11635084 DOI: 10.1186/s40580-024-00462-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Accepted: 11/30/2024] [Indexed: 12/12/2024]
Abstract
The lymphatic system plays a crucial role in maintaining physiological homeostasis and regulating immune responses. Traditional imaging modalities such as magnetic resonance imaging, computerized tomography, and positron emission tomography have been widely used to diagnose disorders in the lymphatic system, including lymphedema, lymphangioma, lymphatic metastasis, and Castleman disease. Nano-fluorescence technology has distinct advantages-including naked-eye visibility, operational simplicity, portability of the laser, and real-time visibility-and serves as an innovative alternative to traditional imaging techniques. This review explores recent advancements in nano-fluorescence imaging aimed at enhancing the resolution of lymphatic structure, function, and immunity. After delineating the fundamental characteristics of lymphatic systems, it elaborates on the development of various nano-fluorescence systems (including nanoparticles incorporating fluorescent dyes and those with intrinsic fluorescence) while addressing key challenges such as photobleaching, limited tissue penetration, biocompatibility, and signal interference from biomolecules. Furthermore, this review highlights the clinical applications of nano-fluorescence and its potential integration into standard diagnostic protocols. Ongoing advancements in nanoparticle technology underscore the potential of nano-fluorescence to revolutionize the diagnosis and treatment of lymphatic disease.
Collapse
Affiliation(s)
- Chae Yeon Han
- School of Integrative Engineering, Chung-Ang University, Seoul, 06974, South Korea
| | - Sang-Hun Choi
- School of Integrative Engineering, Chung-Ang University, Seoul, 06974, South Korea
| | - Soo-Hyang Chi
- School of Integrative Engineering, Chung-Ang University, Seoul, 06974, South Korea
| | - Ji Hyun Hong
- Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, 06591, South Korea
| | - Young-Eun Cho
- Department of Food and Nutrition, Andong National University, Andong, 36729, South Korea
| | - Jihoon Kim
- School of Integrative Engineering, Chung-Ang University, Seoul, 06974, South Korea.
| |
Collapse
|
37
|
Grigoriev V, Korzun T, Moses AS, Jozic A, Zhu X, Kim J, Newton S, Eygeris Y, Diba P, Sattler AL, Levasseur PR, Olson B, Le N, Singh P, Sharma KS, Goo YT, Mamnoon B, Raitmayr C, Mesquita Souza AP, Taratula OR, Sahay G, Marks DL, Taratula O. Targeting Metastasis in Head and Neck Squamous Cell Carcinoma Using Follistatin mRNA Lipid Nanoparticles. ACS NANO 2024; 18:33330-33347. [PMID: 39569532 PMCID: PMC11916978 DOI: 10.1021/acsnano.4c06930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2024]
Abstract
Metastatic progression significantly reduces survival rates and complicates treatment strategies in various cancers. Our study introduces an mRNA therapy for metastasis inhibition by targeting activin A overexpression, a pivotal driver of metastasis and cachexia. Utilizing follistatin mRNA lipid nanoparticles, we effectively downregulated activin A both locally in the tumor environment and systemically. This led to a reduction in tumor burden and suppression of metastatic spread in a murine head and neck squamous cell carcinoma model. Treated mice exhibited minimal metastatic occurrence compared to controls. Additionally, our therapy preserved the cross-sectional area of muscle fibers and adipose tissues, combating the muscle and fat wasting typically observed in cancer-associated cachexia. The therapy also demonstrated a favorable safety profile, underscoring its potential for clinical translation. By integrating metastasis-suppressing and cachexia-alleviating mechanisms, our approach represents a promising advancement in comprehensive cancer management. Considering the widespread upregulation of activin A in many cancer types, our therapy holds considerable potential for application across a broad spectrum of oncologic treatments.
Collapse
Affiliation(s)
- Vladislav Grigoriev
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
| | - Tetiana Korzun
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
- Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, United States
- Medical Scientist Training Program, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, United States
| | - Abraham S Moses
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
| | - Antony Jozic
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
| | - Xinxia Zhu
- Papé Family Pediatric Research Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, United States
| | - Jeonghwan Kim
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
- College of Pharmacy, Yeungnam University, Gyeongsan 38541, Republic of Korea
| | - Samuel Newton
- Papé Family Pediatric Research Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, United States
| | - Yulia Eygeris
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
| | - Parham Diba
- Medical Scientist Training Program, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, United States
| | - Ariana L Sattler
- Cancer Early Detection Advanced Research Center, Knight Cancer Institute, Oregon Health and Science University, 2720 S Moody Ave, Portland, Oregon 97201, United States
| | - Peter R Levasseur
- Papé Family Pediatric Research Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, United States
| | - Brennan Olson
- Medical Scientist Training Program, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, United States
- Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905, United States
| | - Ngoc Le
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
| | - Prem Singh
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
| | - Kongbrailatpam Shitaljit Sharma
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
| | - Yoon Tae Goo
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
| | - Babak Mamnoon
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
| | - Constanze Raitmayr
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
| | - Ana Paula Mesquita Souza
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
| | - Olena R Taratula
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
| | - Gaurav Sahay
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
| | - Daniel L Marks
- Endevica Bio, 1935 Techny Road, Northbrook, Illinois 60062, United States
| | - Oleh Taratula
- Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, 2730 SW Moody Avenue, Portland, Oregon 97201, United States
- Department of Biomedical Engineering, Oregon Health and Science University, 3303 SW Bond Avenue, Portland, Oregon 97239, United States
| |
Collapse
|
38
|
Öztürk K, Kaplan M, Çalış S. Effects of nanoparticle size, shape, and zeta potential on drug delivery. Int J Pharm 2024; 666:124799. [PMID: 39369767 DOI: 10.1016/j.ijpharm.2024.124799] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2024] [Revised: 09/16/2024] [Accepted: 10/02/2024] [Indexed: 10/08/2024]
Abstract
Nanotechnology has brought about a significant revolution in drug delivery, and research in this domain is increasingly focusing on understanding the role of nanoparticle (NP) characteristics in drug delivery efficiency. First and foremost, we center our attention on the size of nanoparticles. Studies have indicated that NP size significantly influences factors such as circulation time, targeting capabilities, and cellular uptake. Secondly, we examine the significance of nanoparticle shape. Various studies suggest that NPs of different shapes affect cellular uptake mechanisms and offer potential advantages in directing drug delivery. For instance, cylindrical or needle-like NPs may facilitate better cellular uptake compared to spherical NPs. Lastly, we address the importance of nanoparticle charge. Zeta potential can impact the targeting and cellular uptake of NPs. Positively charged NPs may be better absorbed by negatively charged cells, whereas negatively charged NPs might perform more effectively in positively charged cells. This review provides essential insights into understanding the role of nanoparticles in drug delivery. The properties of nanoparticles, including size, shape, and charge, should be taken into consideration in the rational design of drug delivery systems, as optimizing these characteristics can contribute to more efficient targeting of drugs to the desired tissues. Thus, research into nanoparticle properties will continue to play a crucial role in the future of drug delivery.
Collapse
Affiliation(s)
- Kıvılcım Öztürk
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Türkiye
| | - Meryem Kaplan
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Türkiye; Department of Pharmaceutical Technology, Faculty of Pharmacy, Süleyman Demirel University, 32260 Isparta, Türkiye
| | - Sema Çalış
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Hacettepe University, 06100 Ankara, Türkiye.
| |
Collapse
|
39
|
El-Saadony MT, Fang G, Yan S, Alkafaas SS, El Nasharty MA, Khedr SA, Hussien AM, Ghosh S, Dladla M, Elkafas SS, Ibrahim EH, Salem HM, Mosa WFA, Ahmed AE, Mohammed DM, Korma SA, El-Tarabily MK, Saad AM, El-Tarabily KA, AbuQamar SF. Green Synthesis of Zinc Oxide Nanoparticles: Preparation, Characterization, and Biomedical Applications - A Review. Int J Nanomedicine 2024; 19:12889-12937. [PMID: 39651353 PMCID: PMC11624689 DOI: 10.2147/ijn.s487188] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 10/17/2024] [Indexed: 12/11/2024] Open
Abstract
Over the last decade, biomedical nanomaterials have garnered significant attention due to their remarkable biological properties and diverse applications in biomedicine. Metal oxide nanoparticles (NPs) are particularly notable for their wide range of medicinal uses, including antibacterial, anticancer, biosensing, cell imaging, and drug/gene delivery. Among these, zinc oxide (ZnO) NPs stand out for their versatility and effectiveness. Recently, ZnO NPs have become a primary material in various sectors, such as pharmaceutical, cosmetic, antimicrobials, construction, textile, and automotive industries. ZnO NPs can generate reactive oxygen species and induce cellular apoptosis, thus underpinning their potent anticancer and antibacterial properties. To meet the growing demand, numerous synthetic approaches have been developed to produce ZnO NPs. However, traditional manufacturing processes often involve significant economic and environmental costs, prompting a search for more sustainable alternatives. Intriguingly, biological synthesis methods utilizing plants, plant extracts, or microorganisms have emerged as ideal for producing ZnO NPs. These green production techniques offer numerous medicinal, economic, environmental, and health benefits. This review highlights the latest advancements in the green synthesis of ZnO NPs and their biomedical applications, showcasing their potential to revolutionize the field with eco-friendly and cost-effective solutions.
Collapse
Affiliation(s)
- Mohamed T El-Saadony
- Department of Agricultural Microbiology, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | - Guihong Fang
- School of Public Health, Heinz Mehlhorn Academician Workstation, Hainan Medical University, Haikou, Hainan, 571199, People’s Republic of China
- Qionghai People’s Hospital, Qionghai, Hainan, 571400, People’s Republic of China
| | - Si Yan
- Qionghai People’s Hospital, Qionghai, Hainan, 571400, People’s Republic of China
| | - Samar Sami Alkafaas
- Molecular Cell Biology Unit, Division of Biochemistry, Department of Chemistry, Faculty of Science, Tanta University, Tanta, 31527, Egypt
| | - Mahmoud A El Nasharty
- Department of Chemistry, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt
| | - Sohila A Khedr
- Industrial Biotechnology Department, Faculty of Science, Tanta University, Tanta, 31733, Egypt
| | - Aya Misbah Hussien
- Biotechnology Department at Institute of Graduate Studies and Research, Alexandria University, Alexandria, 21531, Egypt
| | - Soumya Ghosh
- Natural and Medical Sciences Research Center, University of Nizwa, Nizwa, 616, Oman
| | - Mthokozisi Dladla
- Human Molecular Biology Unit (School of Biomedical Sciences), Faculty of Health Sciences, University of the Free State, Bloemfontein, 9300, South Africa
| | - Sara Samy Elkafas
- Production Engineering and Mechanical Design Department, Faculty of Engineering, Menofia University, Shebin El Kom, Menofia, 32511, Egypt
- Faculty of Control System and Robotics, ITMO University, Saint-Petersburg, 197101, Russia
| | - Essam H Ibrahim
- Biology Department, Faculty of Science, King Khalid University, Abha, 61413, Saudi Arabia
- Blood Products Quality Control and Research Department, National Organization for Research and Control of Biologicals, Cairo, 12611, Egypt
| | - Heba Mohammed Salem
- Department of Poultry Diseases, Faculty of Veterinary Medicine, Cairo University, Giza, 12211, Egypt
| | - Walid F A Mosa
- Plant Production Department (Horticulture-Pomology), Faculty of Agriculture, Saba Basha, Alexandria University, Alexandria, 21531, Egypt
| | - Ahmed Ezzat Ahmed
- Biology Department, Faculty of Science, King Khalid University, Abha, 61413, Saudi Arabia
| | - Dina Mostafa Mohammed
- Nutrition and Food Sciences Department, National Research Centre, Dokki, Giza, 12622, Egypt
| | - Sameh A Korma
- Department of Food Science, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | | | - Ahmed M Saad
- Department of Biochemistry, Faculty of Agriculture, Zagazig University, Zagazig, 44511, Egypt
| | - Khaled A El-Tarabily
- Department of Biology, College of Science, United Arab Emirates University, Al Ain, 15551, United Arab Emirates
| | - Synan F AbuQamar
- Department of Biology, College of Science, United Arab Emirates University, Al Ain, 15551, United Arab Emirates
| |
Collapse
|
40
|
Tan E, Snee PT, Danışman-Kalındemirtaş F. An investigation of quantum dot theranostic probes for prostate and leukemia cancer cells using a CdZnSeS QD-based nanoformulation. J Colloid Interface Sci 2024; 675:1032-1039. [PMID: 39008921 DOI: 10.1016/j.jcis.2024.07.075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2024] [Revised: 07/05/2024] [Accepted: 07/09/2024] [Indexed: 07/17/2024]
Abstract
Anticancer theranostic nanocarriers have the potential to enhance the efficacy of pharmaceutical evaluation of drugs. Semiconductor nanocrystals, also known as quantum dots (QDs), are particularly promising components of drug carrier systems due to their small sizes and robust photoluminescence properties. Herein, bright CdZnSeS quantum dots were synthesized in a single step via the hot injection method. The particles have a quasi-core/shell structure as evident from the high quantum yield (85 %), which decreased to 41 % after water solubilization. These water solubilized QDs were encapsulated into gallic acid / alginate (GA-Alg) matrices to fabricate imaging QDs@mod-PAA/GA-Alg particles with enhanced stability in aqueous media. Cell viability assessments demonstrated that these nanocarriers exhibited viability ranging from 63 % to 83 % across all tested cell lines. Furthermore, the QDs@mod-PAA/GA-Alg particles were loaded with betulinic acid (BA) and ceranib-2 (C2) for in vitro drug release studies against HL-60 leukemia and PC-3 prostate cancer cells. The BA loaded QDs@mod-PAA/GA-Alg had a half-maximal inhibitory concentration (IC50) of 8.76 μg/mL against HL-60 leukemia cells, which is 3-fold lower than that of free BA (IC50 = 26.55 μg/mL). Similar enhancements were observed with nanocarriers loaded with C2 and simultaneously with both BA and C2. Additionally, BA:C2 loaded QDs@mod-PAA/GA-Alg nanocarriers displayed a similar enhancement (IC50 = 3.37 μg/mL compared against IC50 = 11.68 μg/mL for free BA:C2). The C2 loaded QDs@mod-PAA/GA-Alg nanocarriers had an IC50 = 2.24 μg/mL against HL-60 cells. C2 and BA loaded QDs@mod-PAA/GA-Alg NCr had IC50 values of 7.37 μg/mL and 24.55 μg/mL against PC-3 cells, respectively.
Collapse
Affiliation(s)
- Ezgi Tan
- Istanbul University-Cerrahpasa, Department of Chemistry, Istanbul, Turkey.
| | - Preston T Snee
- University of Illinois at Chicago, Department of Chemistry, Chicago, USA.
| | | |
Collapse
|
41
|
Zewail M. Leflunomide nanocarriers: a new prospect of therapeutic applications. J Microencapsul 2024; 41:715-738. [PMID: 39320955 DOI: 10.1080/02652048.2024.2407373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Accepted: 09/17/2024] [Indexed: 09/27/2024]
Abstract
Leflunomide (LEF) is a well-known disease-modifying anti-rheumatic agent (DMARDs) that was approved in 1998 for rheumatoid arthritis (RA) management. It is enzymatically converted into active metabolite teriflunomide (TER) inside the body. LEF and TER possess several pharmacological effects in a variety of diseases including multiple sclerosis, cancer, viral infections and neurobehavioral brain disorders. Despite the aforementioned pharmacological effects exploring these effects in nanomedicine applications has been focused mainly on RA and cancer treatment. This review summarises the main pharmacological, and pharmacokinetic effects of LEF along with highlighting the applications of nanoencapsulation of LEF and its metabolite in different diseases.
Collapse
Affiliation(s)
- Mariam Zewail
- Department of Pharmaceutics, Faculty of Pharmacy, Damanhour University, Damanhour, Egypt
| |
Collapse
|
42
|
Pant A, Laliwala A, Holstein SA, Mohs AM. Recent advances in targeted drug delivery systems for multiple myeloma. J Control Release 2024; 376:215-230. [PMID: 39384153 PMCID: PMC11611669 DOI: 10.1016/j.jconrel.2024.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2024] [Revised: 09/25/2024] [Accepted: 10/02/2024] [Indexed: 10/11/2024]
Abstract
Despite significant therapeutic advances, multiple myeloma (MM) remains a challenging, incurable, hematological malignancy. The efficacy of traditional chemotherapy and currently available anti-MM agents is in part limited by their adverse effects, which restrict their therapeutic potential. Nanotherapeutics is an emerging field of cancer therapy that can overcome the biological and chemical barriers of existing anticancer drugs. This review presents an overview of recent advancements in nanoparticle- and immunotherapy-based drug delivery systems for MM treatment. It further delves into the targeting strategies, mechanism of controlled drug release, and challenges associated with the development of drug delivery systems for the treatment of MM.
Collapse
Affiliation(s)
- Ashruti Pant
- Department of Pharmaceutical Sciences, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA.
| | - Aayushi Laliwala
- Department of Pharmaceutical Sciences, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA.
| | - Sarah A Holstein
- Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; Department of Internal Medicine, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA.
| | - Aaron M Mohs
- Department of Pharmaceutical Sciences, Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, 505 S 45 St, Omaha, NE 68198, USA; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, S 45th St, Omaha, NE 68198, USA.
| |
Collapse
|
43
|
Hameed H, Faheem S, Younas K, Jamshaid M, Ereej N, Hameed A, Munir R, Khokhar R. A comprehensive review on lipid-based nanoparticles via nose to brain targeting as a novel approach. J Microencapsul 2024; 41:681-714. [PMID: 39286884 DOI: 10.1080/02652048.2024.2404414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2024] [Accepted: 09/10/2024] [Indexed: 09/19/2024]
Abstract
The central nervous system (CNS) has been a chief concern for millions of people worldwide, and many therapeutic medications are unable to penetrate the blood-brain barrier. Advancements in nanotechnology have enabled safe, effective, and precise delivery of medications towards specific brain regions by utilising a nose-to-brain targeting route. This method reduces adverse effects, increases medication bioavailability, and facilitates mucociliary clearance while promoting accumulation of drug in the targeted brain region. Recent developments in lipid-based nanoparticles, for instance solid lipid nanoparticles (SLNs), liposomes, nanoemulsions, and nano-structured lipid carriers have been explored. SLNs are currently the most promising drug carrier system because of their capability of transporting drugs across the blood-brain barrier at the intended brain site. This approach offers higher efficacy, controlled drug delivery, target specificity, longer circulation time, and a reduction in toxicity through a biomimetic mechanism.
Collapse
Affiliation(s)
- Huma Hameed
- Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, Pakistan
| | - Saleha Faheem
- Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, Pakistan
| | - Komel Younas
- Faculty of Pharmacy, University Paris Saclay, Orsay, France
| | - Muhammad Jamshaid
- Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, Pakistan
| | - Nelofer Ereej
- Faculty of Pharmaceutical Sciences, University of Central Punjab, Lahore, Pakistan
| | - Anam Hameed
- Department of Human Nutrition and Dietetics, Faculty of Rehabilitation and Allied Health Sciences, Riphah International University, Lahore, Pakistan
| | - Rabia Munir
- Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University Faisalabad, Faisalabad, Pakistan
| | - Rabia Khokhar
- Institute of Pharmaceutical Sciences, University of Veterinary and Animal Sciences, Lahore, Pakistan
| |
Collapse
|
44
|
Ma X, Tian Y, Yang R, Wang H, Allahou LW, Chang J, Williams G, Knowles JC, Poma A. Nanotechnology in healthcare, and its safety and environmental risks. J Nanobiotechnology 2024; 22:715. [PMID: 39548502 PMCID: PMC11566612 DOI: 10.1186/s12951-024-02901-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2024] [Accepted: 10/03/2024] [Indexed: 11/18/2024] Open
Abstract
Nanotechnology holds immense promise in revolutionising healthcare, offering unprecedented opportunities in diagnostics, drug delivery, cancer therapy, and combating infectious diseases. This review explores the multifaceted landscape of nanotechnology in healthcare while addressing the critical aspects of safety and environmental risks associated with its widespread application. Beginning with an introduction to the integration of nanotechnology in healthcare, we first delved into its categorisation and various materials employed, setting the stage for a comprehensive understanding of its potential. We then proceeded to elucidate the diverse healthcare applications of nanotechnology, spanning medical diagnostics, tissue engineering, targeted drug delivery, gene delivery, cancer therapy, and the development of antimicrobial agents. The discussion extended to the current situation surrounding the clinical translation and commercialisation of these cutting-edge technologies, focusing on the nanotechnology-based healthcare products that have been approved globally to date. We also discussed the safety considerations of nanomaterials, both in terms of human health and environmental impact. We presented the in vivo health risks associated with nanomaterial exposure, in relation with transport mechanisms, oxidative stress, and physical interactions. Moreover, we highlighted the environmental risks, acknowledging the potential implications on ecosystems and biodiversity. Lastly, we strived to offer insights into the current regulatory landscape governing nanotechnology in healthcare across different regions globally. By synthesising these diverse perspectives, we underscore the imperative of balancing innovation with safety and environmental stewardship, while charting a path forward for the responsible integration of nanotechnology in healthcare.
Collapse
Affiliation(s)
- Xiaohan Ma
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, Royal Free Hospital, University College London, Rowland Hill Street, London, NW3 2PF, UK.
| | - Yaxin Tian
- United InnoMed (Shanghai) Limited, F/2, E-1, No.299, Kangwei Rd, Pudong District, Shanghai, China
| | - Ren Yang
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, Royal Free Hospital, University College London, Rowland Hill Street, London, NW3 2PF, UK
| | - Haowei Wang
- Centre for Precision Healthcare, UCL Division of Medicine, University College London, London, WC1E 6JF, UK
| | - Latifa W Allahou
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, Royal Free Hospital, University College London, Rowland Hill Street, London, NW3 2PF, UK
- UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
| | - Jinke Chang
- UCL Centre for Biomaterials in Surgical Reconstruction and Regeneration, Division of Surgery & Interventional Science, University College London, London, NW3 2PF, UK
| | - Gareth Williams
- UCL School of Pharmacy, University College London, 29-39 Brunswick Square, London, WC1N 1AX, UK
| | - Jonathan C Knowles
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, Royal Free Hospital, University College London, Rowland Hill Street, London, NW3 2PF, UK
- Department of Nanobiomedical Science and BK21 PLUS NBM Global Research Center for Regenerative Med-Icine, Dankook University, Cheonan, 31116, South Korea
- UCL Eastman-Korea Dental Medicine Innovation Centre, Dankook University, Cheonan, 31116, South Korea
| | - Alessandro Poma
- Division of Biomaterials and Tissue Engineering, Eastman Dental Institute, Royal Free Hospital, University College London, Rowland Hill Street, London, NW3 2PF, UK.
| |
Collapse
|
45
|
Mohammadi Zonouz A, Taghavi S, Nekooei S, Abnous K, Taghdisi SM, Ramezani M, Alibolandi M. Synthesis of targeted doxorubicin-loaded gold nanorod -mesoporous manganese dioxide core-shell nanostructure for ferroptosis, chemo-photothermal therapy in vitro and in vivo. Int J Pharm 2024; 665:124725. [PMID: 39293581 DOI: 10.1016/j.ijpharm.2024.124725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Revised: 09/14/2024] [Accepted: 09/14/2024] [Indexed: 09/20/2024]
Abstract
In the current study, a core-shell inorganic nanostructure comprising a gold nanorod core and -mesoporous manganese dioxide shell was synthesized. Then, the mesoporous manganese dioxide shell was loaded with doxorubicin (DOX) and then coated with pluronic F127 and pluronic F127-folic acid conjugate (1.5:1 wt ratio of pluronic F127: pluronic F127-folic acid conjugate) to prepare targeted final platform. In this design, mesoporous manganese dioxide acted as a reservoir for DOX loading, anti-hypoxia, and MRI contrast agent, while the gold nanorod core acted as a photothermal and CT scan imaging agent. DOX was encapsulated in the mesoporous manganese dioxide shell with a loading capacity and loading efficiency of 19.8 % ± 0.2 and 99.0 % ± 0.9, respectively. The in vitro release experiment showed the impact of glutathione (GSH), mildly acidic pH, and laser irradiating toward accelerated stimuli-responsive DOX release. The ·OH production of the prepared platform was verified by methylene blue (MB) decomposition reaction. Furthermore, thermal imaging exhibited the ability of the prepared platform to convert the NIR irradiation to heat. In vitro cytotoxicity tests on the folate receptor-positive 4 T1 cell line revealed the remarkable cytotoxicity of the targeted formulation compared to the nontargeted formulation (statistically significant). The MTT experiment demonstrated that exposure to laser 808 irradiation enhanced cytotoxicity of the targeted formulation (p < 0.0001). The production of ROS in 4 T1 cells following treatment with the targeted formulation was demonstrated by the dichloro-dihydro-fluorescein diacetate (DCFH-DA) assay. Furthermore, in vivo investigations by implementing subcutaneous 4 T1 tumorized female BABL/c mice indicated that the prepared platform was an effective system in suppressing tumor growth by combining chemotherapy with PTT (photothermal therapy). Additionally, simultanous PTT and anti-hypoxic activity of this system showed potent tumor growth suppression impact. The percent of tumor size reduction in mice treated with FA-F127-DOX@Au-MnO2 + 808 nm laser compared to the control group was 99.7 %. The results of the biodistribution investigation showed tumor accumulation and modified pharmacokinetics of the targeted system. Lastly, 6 and 24 h post-intravenous injection, CT-scan and MR imagings capability of the prepared platform was verified in preclinical stage. The prepared multipurpose system introduces great opportunity to provide multiple treatment strategy along with multimodal imaging capability in a single platform for breast cancer treatment.
Collapse
Affiliation(s)
- Aidin Mohammadi Zonouz
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sahar Taghavi
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Sirous Nekooei
- Department of Radiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Khalil Abnous
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Medicinal Chemistry Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Seyed Mohammad Taghdisi
- Targeted Drug Delivery Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Ramezani
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
| | - Mona Alibolandi
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
| |
Collapse
|
46
|
Sarkar S, Kumar S, Saha G, Basu M, Ghosh MK. Glioma nanotherapy: Unleashing the synergy of dual-loaded DIM and TMZ. Int J Pharm 2024; 665:124697. [PMID: 39270762 DOI: 10.1016/j.ijpharm.2024.124697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2024] [Revised: 08/04/2024] [Accepted: 09/09/2024] [Indexed: 09/15/2024]
Abstract
Glioblastoma multiforme (GBM) is a highly aggressive form of primary brain tumor in adults, which unfortunately has an abysmal prognosis and poor survival rates. The reason behind the poor success rate of several FDA-approved drug is mainly attributed to insufficient drug distribution to the tumor site across the blood-brain barrier (BBB) and induction of resistance. In this study, we have developed a novel nanotherapeutic approach to achieve our goal. PLGA-based nanoencapsulation of both Temozolomide (TMZ) and EGFR inhibitor 3,3'-diindoyl methane (DIM) in a combinatorial approach enhances the delivery of them together. Their synergistic mode of actions, significantly enhances the cytotoxic effect of TMZ in vitro and in vivo. Moreover, the dual-loaded nanoformulation works more efficiently on DNA damage and apoptosis, resulting in a several-fold reduction in tumor burden in vivo, systemic drug toxicity, and increased survival. These findings suggest the preclinical potential of this new treatment strategy.
Collapse
Affiliation(s)
- Sibani Sarkar
- Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector-V, Salt Lake, Kolkata- 700091 & 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India
| | - Sunny Kumar
- Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector-V, Salt Lake, Kolkata- 700091 & 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India; Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh 201 002, India
| | - Gouranga Saha
- Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector-V, Salt Lake, Kolkata- 700091 & 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India
| | - Malini Basu
- Department of Microbiology, Dhruba Chand Halder College, Dakshin Barasat, South 24 Parganas, 743372, India
| | - Mrinal K Ghosh
- Cancer Biology and Inflammatory Disorder Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Biology (CSIR-IICB), TRUE Campus, CN-6, Sector-V, Salt Lake, Kolkata- 700091 & 4, Raja S.C. Mullick Road, Jadavpur, Kolkata 700032, India; Academy of Scientific and Innovative Research, Ghaziabad, Uttar Pradesh 201 002, India.
| |
Collapse
|
47
|
Díaz E, Quezada V, Cifuentes J, Arias Morales NY, Reyes LH, Muñoz-Camargo C, Cruz JC. Enhanced Delivery and Potency of Chemotherapeutics in Melanoma Treatment via Magnetite Nanobioconjugates. ACS OMEGA 2024; 9:45402-45420. [PMID: 39554413 PMCID: PMC11561594 DOI: 10.1021/acsomega.4c07415] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/29/2024] [Accepted: 10/04/2024] [Indexed: 11/19/2024]
Abstract
Melanoma, known for its aggressive metastatic potential, poses significant treatment challenges. Despite the potent antiproliferative effects of anticancer drugs, systemic toxicity and low water solubility limit their efficacy. This study addresses these challenges by employing magnetite (Fe3O4) nanobioconjugates as a drug delivery system, aimed at enhancing drug solubility and reducing off-target effects in melanoma therapy. Magnetite nanoparticles (MNPs) were engineered with functional molecules and loaded with the anticancer agents Temozolomide (TMZ) or paclitaxel (PTX). The nanobioconjugates were characterized via Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), dynamic light scattering (DLS), and transmission electron microscopy (TEM). The results validated the efficacious synthesis and drug loading, attaining efficiencies ranging from 32 to 72% for TMZ and 32 to 60% for PTX. Biocompatibility assessments demonstrated excellent tolerance, with minimal hemolysis rates and platelet aggregation. In vitro studies revealed enhanced cytotoxicity against A-375 human melanoma cells compared to free drugs, with cellular uptake facilitated primarily through macropinocytosis, caveolin-, and clathrin-mediated endocytosis. Furthermore, the nanobioconjugates exhibited significant efficacy in targeting A-375 melanoma spheroids, underlining their potential in melanoma therapy. This research underscores magnetite nanobioconjugates as a promising avenue for targeted melanoma treatment, offering enhanced drug delivery specificity and reduced systemic toxicity in oncological drug delivery systems.
Collapse
Affiliation(s)
- Erika Díaz
- Department
of Biomedical Engineering, Universidad de
Los Andes, Bogotá 111711, Colombia
| | - Valentina Quezada
- Department
of Biomedical Engineering, Universidad de
Los Andes, Bogotá 111711, Colombia
| | - Javier Cifuentes
- Department
of Biomedical Engineering, Universidad de
Los Andes, Bogotá 111711, Colombia
| | - Nydia Yadira Arias Morales
- Center
for Microscopy (MicroCore), Vice Presidency for Research and Creation, Universidad de Los Andes, Bogotá 111711, Colombia
| | - Luis H. Reyes
- Product
and Process Design Group (GDPP), Department of Chemical and Food Engineering, Universidad de Los Andes, Bogotá 111711, Colombia
| | | | - Juan C. Cruz
- Department
of Biomedical Engineering, Universidad de
Los Andes, Bogotá 111711, Colombia
| |
Collapse
|
48
|
Kwon WA. FGFR Inhibitors in Urothelial Cancer: From Scientific Rationale to Clinical Development. J Korean Med Sci 2024; 39:e320. [PMID: 39536791 PMCID: PMC11557252 DOI: 10.3346/jkms.2024.39.e320] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 10/10/2024] [Indexed: 11/16/2024] Open
Abstract
In the past decade, the treatment of metastatic urothelial cancer (mUC), including bladder cancer (BC), has transformed significantly with the introduction of diverse therapies, such as immune checkpoint inhibitors, targeted therapies, and antibody-drug conjugates. This change is partly due to advancements in genomic understanding, particularly next-generation sequencing, which has identified numerous mutations in UC. Among these therapies, erdafitinib, a pan-fibroblast growth factor receptor (FGFR) inhibitor for specific FGFR2 and FGFR3 alterations, is the only targeted therapy approved till now. In 2019, erdafitinib became pivotal for the treatment of mUC, particularly in patients with specific FGFR alterations. Recent studies have highlighted the benefits of combining erdafitinib with immunotherapy, thereby broadening the treatment options. Ongoing investigations exist on its use in non-muscle-invasive BC and in combination with drugs such as enfortumab vedotin in mUC. Other FGFR-targeted agents are under development; however, overcoming FGFR resistance and ensuring the safety of combination therapies remain major hurdles. FGFR3 mutations are particularly prevalent in BC, a heterogeneous form of UC, and account for a considerable proportion of new cancer diagnoses annually. Approximately half of these cancers have FGFR3 mutations, with gene rearrangements being a common feature. These FGFR3 genomic alterations often occur independently of mutations in other BC oncogenes, such as TP53 and RB1. This review emphasizes the importance of FGFR inhibition in UC and the optimization of its use in clinical practice. Moreover, it underscores the ongoing efforts to evaluate combination strategies and early treatment testing to enhance the effectiveness of targeted therapies for UC.
Collapse
MESH Headings
- Humans
- Urinary Bladder Neoplasms/drug therapy
- Urinary Bladder Neoplasms/pathology
- Urinary Bladder Neoplasms/genetics
- Urinary Bladder Neoplasms/metabolism
- Receptor, Fibroblast Growth Factor, Type 3/antagonists & inhibitors
- Receptor, Fibroblast Growth Factor, Type 3/genetics
- Receptor, Fibroblast Growth Factor, Type 3/metabolism
- Pyrazoles/therapeutic use
- Mutation
- Receptor, Fibroblast Growth Factor, Type 2/antagonists & inhibitors
- Receptor, Fibroblast Growth Factor, Type 2/genetics
- Receptor, Fibroblast Growth Factor, Type 2/metabolism
- Quinoxalines/therapeutic use
- Antineoplastic Agents/therapeutic use
- Antineoplastic Agents/pharmacology
- Antibodies, Monoclonal/therapeutic use
- Protein Kinase Inhibitors/therapeutic use
- Protein Kinase Inhibitors/pharmacology
- Immunotherapy
- Receptors, Fibroblast Growth Factor/antagonists & inhibitors
- Receptors, Fibroblast Growth Factor/metabolism
- Receptors, Fibroblast Growth Factor/genetics
Collapse
Affiliation(s)
- Whi-An Kwon
- Department of Urology, Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea.
| |
Collapse
|
49
|
Gómez-González E, Caro C, Núñez NO, González-Mancebo D, Urbano-Gámez JD, García-Martín ML, Ocaña M. Sodium lanthanide tungstate-based nanoparticles as bimodal contrast agents for in vivo high-field MRI and CT imaging. J Mater Chem B 2024; 12:11123-11133. [PMID: 39268755 DOI: 10.1039/d4tb01157k] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/15/2024]
Abstract
Research on high-field magnetic resonance imaging (HF-MRI) has been increased in recent years, aiming to improve diagnosis accuracy by increasing the signal-to-noise ratio and hence image quality. Conventional contrast agents (CAs) have important limitations for HF-MRI, with the consequent need for the development of new CAs. Among them, the most promising alternatives are those based on Dy3+ or Ho3+ compounds. Notably, the high atomic number of lanthanide cations would bestow a high capability for X-ray attenuation to such Dy or Ho-based compounds, which would also allow them to be employed as CAs for X-ray computed tomography (CT). In this work, we have prepared uniform NaDy(WO4)2 and NaHo(WO4)2 nanoparticles (NPs), which were dispersible under conditions that mimic the physiological media and were nontoxic for cells, meeting the main requirements for their use in vivo. Both NPs exhibited satisfactory magnetic relaxivities at 9.4 T, thus making them a promising alternative to clinical CAs for HF-MRI. Furthermore, after their intravenous administration in tumor-bearing mice, both NPs exhibited significant accumulation inside the tumor at 24 h, attributable to passive targeting by the enhanced permeability and retention (EPR) effect. Therefore, our NPs are suitable for the detection of tumors through HF-MRI. Finally, NaDy(WO4)2 NPs showed a superior X-ray attenuation capability than iohexol (commercial CT CA), which, along with their high r2 value, makes them suitable as the dual-probe for both HF-MRI and CT imaging, as demonstrated by in vivo experiments conducted using healthy mice.
Collapse
Affiliation(s)
- Elisabet Gómez-González
- Instituto de Ciencia de Materiales de Sevilla (CSIC-US), c/Américo Vespucio, 49, 41092 Sevilla, Spain.
| | - Carlos Caro
- Biomedical Magnetic Resonance Laboratory-BMRL, Andalusian Public Foundation Progress and Health-FPS, Seville, Spain
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, C/Severo Ochoa, 35, 29590 Malaga, Spain
| | - Nuria O Núñez
- Instituto de Ciencia de Materiales de Sevilla (CSIC-US), c/Américo Vespucio, 49, 41092 Sevilla, Spain.
| | - Daniel González-Mancebo
- Instituto de Ciencia de Materiales de Sevilla (CSIC-US), c/Américo Vespucio, 49, 41092 Sevilla, Spain.
| | - Jesús D Urbano-Gámez
- Biomedical Magnetic Resonance Laboratory-BMRL, Andalusian Public Foundation Progress and Health-FPS, Seville, Spain
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, C/Severo Ochoa, 35, 29590 Malaga, Spain
| | - Maria L García-Martín
- Biomedical Magnetic Resonance Laboratory-BMRL, Andalusian Public Foundation Progress and Health-FPS, Seville, Spain
- Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina-IBIMA Plataforma Bionand, C/Severo Ochoa, 35, 29590 Malaga, Spain
- Biomedical Research Networking Center in Bioengineering, Biomaterials & Nanomedicine (CIBER-BBN), 28029 Madrid, Spain
| | - Manuel Ocaña
- Instituto de Ciencia de Materiales de Sevilla (CSIC-US), c/Américo Vespucio, 49, 41092 Sevilla, Spain.
| |
Collapse
|
50
|
Zhao W, Li Q, He P, Li C, Aryal M, Fabiilli ML, Xiao H. Charge balanced aggregation: A universal approach to aqueous organic nanocrystals. J Control Release 2024; 375:552-573. [PMID: 39276800 DOI: 10.1016/j.jconrel.2024.09.017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2024] [Revised: 09/08/2024] [Accepted: 09/10/2024] [Indexed: 09/17/2024]
Abstract
Organic nanocrystals, particularly those composed of conjugated molecules, hold immense potential for various applications. However, their practical utility is often hindered by the challenge of achieving stable aqueous dispersions, which are essential for biological compatibility and effective delivery. This study introduces a novel and versatile strategy for preparing stable aqueous organic nanocrystals using a modified reprecipitation method. We demonstrate the broad applicability of this approach by successfully preparing a diverse library of nanocrystals from 27 conjugated molecules. Our findings reveal a charge-balanced aggregation mechanism for nanocrystal formation, highlighting the crucial role of surface charge in controlling particle size and stability. Based on this mechanism, we establish a comprehensive molecular combination strategy that directly links molecular properties to colloidal behaviour, enabling the straightforward prediction and preparation of stable aqueous dispersions without the need for excipients. This strategy provides a practical workflow for tailoring the functionality of these nanocrystals for a wide range of applications. To illustrate their therapeutic potential, we demonstrate the enhanced efficacy of these nanocrystals in treating acute ulcerative colitis, myocardial ischemia/reperfusion injury, and cancer in mouse models. This work paves the way for developing next-generation nanomaterials with tailored functionalities for diverse biomedical applications.
Collapse
Affiliation(s)
- Wenwen Zhao
- School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong, China
| | - Qiu Li
- College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao 266000, Shandong, China
| | - Peng He
- School of Basic Medicine, Qingdao University, Qingdao 266071, Shandong, China
| | - Changqing Li
- Department of Electrical Engineering, University of California Merced, Merced 95343, CA, USA
| | - Muna Aryal
- Chemical, Biological, and Bioengineering Department, College of Engineering, North Carolina Agricultural and Technical State University, Greensboro 27411, NC, USA
| | - Mario L Fabiilli
- Department of Biomedical Engineering, University of Michigan, Ann Arbor 48109, MI, USA; Applied Physics Program, University of Michigan, Ann Arbor, 48109, MI, USA; Department of Radiology, University of Michigan, Ann Arbor, 48109, MI, USA
| | - Haijun Xiao
- Department of Radiology, University of Michigan, Ann Arbor, 48109, MI, USA.
| |
Collapse
|