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Kumar Sahdev A, Raorane CJ, Ali MA, Mashay Al-Anazi K, Manoharan RK, Raj V, Singh A. Chitosan-Folic Acid-Coated Quercetin-Loaded PLGA Nanoparticles for Hepatic Carcinoma Treatment. Polymers (Basel) 2025; 17:955. [PMID: 40219344 PMCID: PMC11991491 DOI: 10.3390/polym17070955] [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: 03/17/2025] [Accepted: 03/27/2025] [Indexed: 04/14/2025] Open
Abstract
Hepatocellular carcinoma (HCC) causes the third highest mortality worldwide. Liver ablation, surgery, and embolization are conventional methods for treatment. However, these methods have limitations. To overcome these issues, nanomedicines have potential due to their high stability, high drug load capacity, and controlled release. Thus, we prepared quercetin-loaded polylactic-co-glycolic acid (PLGA) nanoparticles coated with folic acid-chitosan (QPCF-NPs) to improve drug delivery and targetability applications of quercetin for the treatment of HCC. We prepared QPCF-NPs by solvent evaporation and coated them with chitosan-folic acid (CS-FA). QPCF-NPs were examined using Fourier-Transform infrared (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X-ray diffraction (XRD). In addition, the drug release rate and cytotoxicity were studied. Moreover, in vivo HCC studies such as histopathology and biochemical parameters were conducted. Subsequently, QPCF-NPs with a spherical shape and an average size of 200-290 nm have been demonstrated to have formed by FTIR, XRD, SEM, and TEM. Further, we observed sustained drug release from QPCF-NPs compared to quercetin. Cellular cytotoxicity showed significant inhibition in the HEPG2-cell line with QPCF-NPs treatment. Biochemical estimate and oxidative stress regulation were considerably more regulated in the treatment groups than the HCC group in a dose-dependent way after subcutaneous administration of QPCF-NPs. ELISA of interleukin and caspase-3 demonstrated the anticipated results in comparison to the carcinogen control group. Compared to earlier preparations, the QPCF-NPs generated demonstrated better drug targetability and potency for treating HCC.
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Affiliation(s)
- Anil Kumar Sahdev
- Department of Pharmaceutical Sciences, Faculty of Technology, Sir J.C. Bose Technical Campus, Kumaun University, Nainital 263136, Uttarakhand, India;
| | | | - Mohammad Ajmal Ali
- Department of Botany and Microbiology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | - Khalid Mashay Al-Anazi
- Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia
| | | | - Vinit Raj
- School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea;
| | - Anita Singh
- Department of Pharmaceutical Sciences, Faculty of Technology, Sir J.C. Bose Technical Campus, Kumaun University, Nainital 263136, Uttarakhand, India;
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Kooshan Z, Srinivasan S, Janjua TI, Popat A, Batra J. Lactoferrin conjugated radicicol nanoparticles enhanced drug delivery and cytotoxicity in prostate cancer cells. Eur J Pharmacol 2025; 991:177300. [PMID: 39870236 DOI: 10.1016/j.ejphar.2025.177300] [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: 03/13/2024] [Revised: 01/16/2025] [Accepted: 01/22/2025] [Indexed: 01/29/2025]
Abstract
Pyruvate dehydrogenase kinase-1 (PDK1) plays a crucial role in cancer cell metabolism by regulating the glycolytic pathway. Although, inhibitors targeting PDK1 have been effective in inhibiting glycolysis in multiple cancers, their lack of selectivity leading to off-target effects limit their therapeutic benefit. Herein, we investigated the inhibitory potential of six PDK1 inhibitors on cellular proliferation, migration, and invasion of androgen-sensitive LNCaP and androgen-negative PC-3 prostate cancer cells. Of the six PDK1 inhibitors, radicicol and dicumarol significantly inhibited cellular proliferation and exhibited lower metabolic activity in both LNCaP and PC-3 metastatic prostate cancer cells. Radicicol was highly effective at lower concentration. Moreover, radicicol significantly inhibited migration and invasion in PC-3 cells. We then developed a lactoferrin nanoparticle (LF-NP) encapsulated with Radicicol (Ra-LF-NP), using a rotary evaporation method. Spheroid assays confirmed the higher inhibitory potential of Ra-LF-NP with a reduction in spheroid area by 80%, and invasiveness compared to radicicol alone. Lactoferrin receptors are overexpressed on the surface of many cancer cells, including prostate cancer. Conjugating radicicol with lactoferrin nanoparticles, potentially enhanced the specific uptake of the drug by prostate cancer cells while minimizing the off-target effects on healthy cells. This targeted therapy approach could lead to improved treatment outcomes and reduced side effects. Our study demonstrated the potential of radicicol delivery by lactoferrin-conjugated nanoparticle as an efficient drug delivery strategy for prostate cancer treatment.
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Affiliation(s)
- Zeinab Kooshan
- School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; Translational Research Institute, Queensland University of Technology, Brisbane, Australia
| | - Srilakshmi Srinivasan
- School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; Translational Research Institute, Queensland University of Technology, Brisbane, Australia; Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia
| | | | - Amirali Popat
- School of Pharmacy, The University of Queensland, Brisbane, Australia
| | - Jyotsna Batra
- School of Biomedical Sciences, Faculty of Health, Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia; Translational Research Institute, Queensland University of Technology, Brisbane, Australia; Centre for Genomics and Personalised Health, Queensland University of Technology, Brisbane, Queensland, Australia.
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Mohapatra P, Chandrasekaran N. In vitro β-catenin attenuation by a mefloquine-loaded core-shell nano emulsion strategy to suppress liver cancer cells. NANOSCALE ADVANCES 2025; 7:748-765. [PMID: 39610791 PMCID: PMC11601157 DOI: 10.1039/d4na00547c] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/04/2024] [Accepted: 10/26/2024] [Indexed: 11/30/2024]
Abstract
Liver cancer, with its robust metastatic propensity, imposes a substantial global health burden of around 800 000 new cases annually. Mutations in the Wnt/β-catenin pathway genes are common in liver cancer, driving over 80% of cases. Targeting this pathway could potentially lead to better treatments. The aim of the present study was to develop a novel strategy for targeting the Wnt/β-catenin pathway while blocking the growth and division, of liver cancer cells and downregulating gene expression. This was achieved by formulating a repurposed drug (mefloquine)-loaded garlic nano-emulsion (GNE) with gold nanoparticles (GNPs) as a core-shell nano-emulsion (MQ/GNE-GNP). The biocompatible core-shell nano-emulsion (MQ/GNE-GNP) exhibited a size distribution in the range of 50-100 nm, high stability, excellent hydrophilicity, good biosafety, and sustained release. Human liver cancer cells were exposed to MQ/GNE, GNPs, and MQ/GNE-GNP at varying concentrations, and the effects were assessed through analysis of the cytotoxicity, reactive oxygen species, cell death, cell cycle analysis, and gene expression studies. It was found that MQ/GNE-GNP arrested HepG2 cells in the sub G0/G1phase and induced apoptosis. The anticancer efficacy of the core-shell nano-emulsion (MQ/GNE-GNP) resulted in higher cell death in the AO/PI staining studies, demonstrating its greater anticancer efficacy. The administration of MQ/GNE-GNP downregulated the overall expression of nuclear β-catenin, thereby suppressing the Wnt/β-catenin pathway. The protein expression level of Wnt 1 was upregulated, while β-catenin expression was significantly decreased. The core-shell nano-emulsion, incorporating a repurposed drug, could disrupt the β-catenin connections in the Wnt/β-catenin pathway. In conclusion, MQ/GNE-GNP could be a promising core-shell nano emulsion for the effective treatment of liver cancer by targeting the Wnt/β-catenin pathway.
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Affiliation(s)
- Priyadarshini Mohapatra
- ICMR-SRF, Centre for Nanobiotechnology, Vellore Institute of Technology Vellore 632014 India
| | - Natarajan Chandrasekaran
- Centre for Nanobiotechnology, VIT University Vellore 632 014 India +91-416-2243092 +91-416-220-2879
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Fan Y, Xiao H, Wang Y, Wang S, Sun H. Global research on nanomaterials for liver cancer from 2004 to 2023: a bibliometric and visual analysis. Discov Oncol 2024; 15:838. [PMID: 39722094 DOI: 10.1007/s12672-024-01735-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 12/19/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND Primary liver cancer, particularly hepatocellular carcinoma, is one of the most common gastrointestinal cancers. An increasing number of studies indicate that nanomaterials play a significant role in the diagnosis and treatment of liver cancer. However, despite the extensive and diverse research on nanomaterials and liver cancer, bibliometric studies in this field have not yet been reported. This study aims to comprehensively evaluate the application prospects and development trends of nanomaterials in primary liver cancer over the past 20 years. By elucidating the current state of research on liver cancer, we intend to provide valuable reference information for researchers in this field. METHODS We conducted a comprehensive search of the Web of Science Core Collection for publications related to liver cancer and nanomaterials from January 1, 2004, to December 31, 2023. Relevant literature was selected based on specific inclusion and exclusion criteria. These selected publications were subsequently analyzed using CiteSpace, VOSviewer, and the R package "bibliometrix" to identify trends, influential countries, institutions, authors, journals, and research hotspots in this field. RESULTS This study included a total of 1641 publications, with an annual growth rate of 25.45%. China and the United States are leading in this field, accounting for 67.46% and 11.27% of the total publications, respectively. The Chinese Academy of Sciences and Shao D are the most cited institution and author, respectively. The International Journal of Nanomedicine is the most influential journal in this field, while Biomaterials is the most highly cited and co-cited journal. Research hotspots mainly focus on improving drug delivery efficiency, inducing cancer cell apoptosis, photodynamic therapy, photothermal therapy, and combination treatments. Emerging research directions include the tumor microenvironment, polyethylene glycol, and immunogenic cell death. CONCLUSION The results of this study indicate that the application of nanomaterials in the field of liver cancer is gradually becoming a significant research area, with a focus on improving drug delivery efficiency, enhancing therapeutic efficacy, and reducing side effects.
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Affiliation(s)
- Yitao Fan
- Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China
- Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Han Xiao
- Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China
- Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Yan Wang
- Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China
- Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Shuhan Wang
- Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China
- Lanzhou University, Lanzhou, 730030, Gansu, China
| | - Hui Sun
- Cuiying Biomedical Research Center, The Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, 730030, Gansu, China.
- Lanzhou University, Lanzhou, 730030, Gansu, China.
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Lin M, Lv X, Wang H, Shu L, Wang H, Zhang G, Sun J, Chen X. Coacervation-Driven Semipermeable Nanoreactors for Enzymatic Cascade-Mediated Cancer Combination Therapy with Enhanced Efficacy. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2024; 36:e2407378. [PMID: 39235373 DOI: 10.1002/adma.202407378] [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] [Received: 05/23/2024] [Revised: 08/13/2024] [Indexed: 09/06/2024]
Abstract
Utilizing enzyme cascades as a promising approach for targeted cancer therapies holds significant potential, yet its clinical effectiveness is substantially hindered by functional losses during delivery. Complex coacervation emerges as an intriguing strategy for designing functional nanoreactors. In this study, a noteworthy achievement is presented in the development of lactobionic acid-modified tumor microenvironment (TME)-responsive polyelectrolyte complex vesicles (HGS-PCVs) based on bioinspired homopolypeptoids, which serve as a facile, intelligent, and highly efficient nanoreactor tunable for glucose oxidase, hemoglobin, and sorafenib (SRF) to hepatic cancer cells. The TME-responsive permeability of HGS-PCVs enables the selective entry of glucose into their interior, triggering an enzymatic cascade reaction within the tumor. This intricate process generates toxic hydroxyl radicals while concurrently lowering the pH. Consequently, this pH shift enhances the SRF release, effectively promoting ferroptosis and apoptosis in the target cancer cells. Further, the administration of the HGS-PCVs not only initiates immunogenic cell death but also plays a crucial role in inducing the maturation of dendritic cells within lymph nodes. It stimulates an adaptive T-cell response, a crucial mechanism that contributes to impeding the growth of distant tumors in vivo, demonstrating the promising potential of PCVs for cancer immunotherapy.
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Affiliation(s)
- Min Lin
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, 130012, P. R. China
| | - Xueli Lv
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, 130012, P. R. China
| | - Hepeng Wang
- China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, P. R. China
| | - Lilei Shu
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, 130012, P. R. China
| | - Helin Wang
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, 130012, P. R. China
| | - Guojing Zhang
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, 130012, P. R. China
| | - Jing Sun
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, 130012, P. R. China
| | - Xuesi Chen
- State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun, Jilin, 130012, P. R. China
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Rajesh R U, Sangeetha D. Therapeutic potentials and targeting strategies of quercetin on cancer cells: Challenges and future prospects. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 133:155902. [PMID: 39059266 DOI: 10.1016/j.phymed.2024.155902] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 07/08/2024] [Accepted: 07/19/2024] [Indexed: 07/28/2024]
Abstract
BACKGROUND Every cell in the human body is vital because it maintains equilibrium and carries out a variety of tasks, including growth and development. These activities are carried out by a set of instructions carried by many different genes and organized into DNA. It is well recognized that some lifestyle decisions, like using tobacco, alcohol, UV, or multiple sexual partners, might increase one's risk of developing cancer. The advantages of natural products for any health issue are well known, and researchers are making attempts to separate flavonoid-containing substances from plants. Various parts of plants contain a phenolic compound called flavonoid. Quercetin, which belongs to the class of compounds known as flavones with chromone skeletal structure, has anti-cancer activity. PURPOSE The study was aimed at investigating the therapeutic action of the flavonoid quercetin on various cancer cells. METHODS The phrases quercetin, anti-cancer, nanoparticles, and cell line were used to search the data using online resources such as PubMed, and Google Scholar. Several critical previous studies have been included. RESULTS Quercetin inhibits various dysregulated signaling pathways that cause cancer cells to undergo apoptosis to exercise its anticancer effects. Numerous signaling pathways are impacted by quercetin, such as the Hedgehog system, Akt, NF-κB pathway, downregulated mutant p53, JAK/STAT, G1 phase arrest, Wnt/β-Catenin, and MAPK. There are downsides to quercetin, like hydrophobicity, first-pass effect, instability in the gastrointestinal tract, etc., because of which it is not well-established in the pharmaceutical industry. The solution to these drawbacks in the future is using bio-nanomaterials like chitosan, PLGA, liposomes, and silk fibroin as carriers, which can enhance the target specificity of quercetin. The first section of this review covers the specifics of flavonoids and quercetin; the second section covers the anti-cancer activity of quercetin; and the third section explains the drawbacks and conjugation of quercetin with nanoparticles for drug delivery by overcoming quercetin's drawback. CONCLUSIONS Overall, this review presented details about quercetin, which is a plant derivative with a promising molecular mechanism of action. They inhibit cancer by various mechanisms with little or no side effects. It is anticipated that plant-based materials will become increasingly relevant in the treatment of cancer.
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Affiliation(s)
- Udaya Rajesh R
- Department of Chemistry, School of Advanced Science, Vellore Institute of Technology, Vellore, 632014 Tamil Nadu, India
| | - Dhanaraj Sangeetha
- Department of Chemistry, School of Advanced Science, Vellore Institute of Technology, Vellore, 632014 Tamil Nadu, India.
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Fan QQ, Tian H, Cheng JX, Zou JB, Luan F, Qiao JX, Zhang D, Tian Y, Zhai BT, Guo DY. Research progress of sorafenib drug delivery system in the treatment of hepatocellular carcinoma: An update. Biomed Pharmacother 2024; 177:117118. [PMID: 39002440 DOI: 10.1016/j.biopha.2024.117118] [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: 04/09/2024] [Revised: 07/01/2024] [Accepted: 07/08/2024] [Indexed: 07/15/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant tumors in the contemporary era, representing a significant global health concern. Early HCC patients have mild symptoms or are asymptomatic, which promotes the onset and progression of the disease. Moreover, advanced HCC is insensitive to chemotherapy, making traditional clinical treatment unable to block cancer development. Sorafenib (SFB) is a first-line targeted drug for advanced HCC patients with anti-angiogenesis and anti-tumor cell proliferation effects. However, the efficacy of SFB is constrained by its off-target distribution, rapid metabolism, and multi-drug resistance. In recent years, nanoparticles based on a variety of materials have been demonstrated to enhance the targeting and therapeutic efficacy of SFB against HCC. Concurrently, the advent of joint drug delivery systems has furnished crucial empirical evidence for reversing SFB resistance. This review will summarize the application of nanotechnology in the field of HCC treatment over the past five years. It will focus on the research progress of SFB delivery systems combined with multiple therapeutic modalities in HCC treatment.
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Affiliation(s)
- Qiang-Qiang Fan
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Huan Tian
- Xi'an Hospital of Traditional Chinese Medicine, 710021, China
| | - Jiang-Xue Cheng
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Jun-Bo Zou
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Fei Luan
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Jia-Xin Qiao
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Dan Zhang
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Yuan Tian
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China
| | - Bing-Tao Zhai
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China.
| | - Dong-Yan Guo
- State Key Laboratory of Research & Development of Characteristic Qin Medicine Resources (Cultivation), and Shaanxi Key Laboratory of Chinese Medicine Fundamentals and New Drugs Research, and Shaanxi Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Shaanxi University of Chinese Medicine, Xi'an 712046, China.
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Selvaraj S, Chauhan A, Verma R, Dutta V, Rana G, Duglet R, Subbarayan R, Batoo KM. Role of degrading hydrogels in hepatocellular carcinoma drug delivery applications: A review. J Drug Deliv Sci Technol 2024; 95:105628. [DOI: 10.1016/j.jddst.2024.105628] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Kabil MF, Gaber SAA, Hamzawy MA, El-Sherbiny IM, Nasr M. Folic/lactobionic acid dual-targeted polymeric nanocapsules for potential treatment of hepatocellular carcinoma. Drug Deliv Transl Res 2024; 14:1338-1351. [PMID: 37930630 DOI: 10.1007/s13346-023-01467-9] [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] [Accepted: 10/28/2023] [Indexed: 11/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor that affects many patients diagnosed with hepatic cell inflammation and liver cirrhosis. Targeted polymeric nanocapsules could facilitate the internalization and accumulation of anticancer drugs. Dual-targeted folic acid/lactobionic acid-poly lactic co-glycolic acid nanocapsules (NCs) were prepared and loaded with pterostilbene (PTN) and characterized for their physicochemical properties, as well as in vitro and in vivo anticancer activity. NCs displayed a size of 222 nm, zeta potential of - 16.5 mV, and sustained release for 48 h. The IC50 of PTN NCs (5.87 ± 0.8 µg/mL) was 20 times lower than unencapsulated PTN (121.26 ± 9.42 µg/mL) on HepG2 liver cancer cells owing to the enhanced cellular uptake of the former, as delineated by flow cytometry. In vivo study on HCC-induced animals delineated the superiority of the dual-targeted NCs over the unencapsulated PTN, which significantly reduced the liver markers ALT, AST, and ALP, as well as the tumor-related markers AFP and Bcl2, and elevated the anti-apoptotic marker caspase 3. Furthermore, the NCs significantly reduced the oxidative stress and exhibited almost comparable histological features to the normal group. Therefore, it can be concluded that the dual-ligated folic acid/lactobionic acid nanocapsules can be considered a promising potential treatment option for hepatocellular carcinoma.
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Affiliation(s)
- Mohamed Fawzi Kabil
- Nanomedicine Research Labs, Center for Materials Science, Zewail City of Science and Technology, Giza, Egypt
| | - Sara A Abdel Gaber
- Nanomedicine Department, Institute of Nanoscience and Nanotechnology, Kafr Elsheikh University, Kafr Elsheikh, Egypt
| | - Mohamed A Hamzawy
- Pharmacology and Toxicology Department, Faculty of Pharmacy, Fayoum University, Fayoum, Egypt
| | - Ibrahim M El-Sherbiny
- Nanomedicine Research Labs, Center for Materials Science, Zewail City of Science and Technology, Giza, Egypt
| | - Maha Nasr
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
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Kabil MF, Badary OA, Bier F, Mousa SA, El-Sherbiny IM. A comprehensive review on lipid nanocarrier systems for cancer treatment: fabrication, future prospects and clinical trials. J Liposome Res 2024; 34:135-177. [PMID: 37144339 DOI: 10.1080/08982104.2023.2204372] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Accepted: 04/02/2023] [Indexed: 05/06/2023]
Abstract
Over the last few decades, cancer has been considered a clinical challenge, being among the leading causes of mortality all over the world. Although many treatment approaches have been developed for cancer, chemotherapy is still the most utilized in the clinical setting. However, the available chemotherapeutics-based treatments have several caveats including their lack of specificity, adverse effects as well as cancer relapse and metastasis which mainly explains the low survival rate of patients. Lipid nanoparticles (LNPs) have been utilized as promising nanocarrier systems for chemotherapeutics to overcome the challenges of the currently applied therapeutic strategies for cancer treatment. Loading chemotherapeutic agent(s) into LNPs improves drug delivery at different aspects including specific targeting of tumours, and enhancing the bioavailability of drugs at the tumour site through selective release of their payload, thus reducing their undesired side effects on healthy cells. This review article delineates an overview of the clinical challenges in many cancer treatments as well as depicts the role of LNPs in achieving optimal therapeutic outcomes. Moreover, the review contains a comprehensive description of the many LNPs categories used as nanocarriers in cancer treatment to date, as well as the potential of LNPs for future applications in other areas of medicine and research.
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Affiliation(s)
- Mohamed Fawzi Kabil
- Nanomedicine Research Labs, Center for Materials Science (CMS), Zewail City of Science and Technology, Giza, Egypt
| | - Osama A Badary
- Clinical Pharmacy Department, Faculty of Pharmacy, The British University in Egypt, El-Shorouk City, Egypt
| | - Frank Bier
- AG Molekulare Bioanalytik und Bioelektronik, Institut für Biochemie und Biologie, Universität Potsdam Karl-Liebknecht-Straße 24/25, Potsdam (OT Golm), Germany
| | - Shaker A Mousa
- Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY, USA
| | - Ibrahim M El-Sherbiny
- Nanomedicine Research Labs, Center for Materials Science (CMS), Zewail City of Science and Technology, Giza, Egypt
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Zhou XQ, Li YP, Dang SS. Precision targeting in hepatocellular carcinoma: Exploring ligand-receptor mediated nanotherapy. World J Hepatol 2024; 16:164-176. [PMID: 38495282 PMCID: PMC10941735 DOI: 10.4254/wjh.v16.i2.164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 01/10/2024] [Accepted: 01/18/2024] [Indexed: 02/27/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality. Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages, but it is often ineffective and suffers from problems such as multidrug resistance, rapid drug clearance, nonspecific targeting, high side effects, and low drug accumulation in tumor cells. In response to these limitations, recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC. This review focuses on recent advances in nanoparticle-based targeted drug delivery systems, with special attention to various receptors overexpressed on HCC cells. These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC. We comprehensively summarize the current understanding of these receptors, their role in nanoparticle targeting, and the impact of such targeted therapies on HCC. By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies, more effective and precise treatment of HCC can be achieved.
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Affiliation(s)
- Xia-Qing Zhou
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Ya-Ping Li
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Shuang-Suo Dang
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
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12
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Ji G, Li Y, Zhang Z, Li H, Sun P. Recent advances of novel targeted drug delivery systems based on natural medicine monomers against hepatocellular carcinoma. Heliyon 2024; 10:e24667. [PMID: 38312669 PMCID: PMC10834828 DOI: 10.1016/j.heliyon.2024.e24667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 12/22/2023] [Accepted: 01/11/2024] [Indexed: 02/06/2024] Open
Abstract
Hepatocellular carcinoma (HCC), the most prevalent type of liver cancer, is often diagnosed at an advanced stage. Surgical interventions are often ineffective, leading HCC patients to rely on systemic chemotherapy. Unfortunately, commonly used chemotherapeutic drugs have limited efficacy and can adversely affect vital organs, causing significant physical and psychological distress for patients. Natural medicine monomers (NMMs) have shown promising efficacy and safety profiles in HCC treatment, garnering attention from researchers. In recent years, the development of novel targeted drug delivery systems (TDDS) combining NMMs with nanocarriers has emerged. These TDDS aim to concentrate drugs effectively in HCC cells by manipulating the characteristics of nanomedicines, leveraging receptor and ligand interactions, and utilizing endogenous stimulatory responses to promote specific nanomedicines distribution. This comprehensive review presents recent research on TDDS for HCC treatment using NMMs from three perspectives: passive TDDS, active TDDS, and stimuli-responsive drug delivery systems (SDDS). It consolidates the current state of research on TDDS for HCC treatment with NMMs and highlights the potential of these innovative approaches in improving treatment outcomes. Moreover, the review also identifies research gaps in the related fields to provide references for future targeted therapy research in HCC.
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Affiliation(s)
- Guanjie Ji
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Yue Li
- Department of Clinical Pharmacy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Zhiyue Zhang
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong Province, 250012, China
| | - Hui Li
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong Province, 250012, China
| | - Ping Sun
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
- Grade Three Laboratory of Traditional Chinese Medicine Preparation of the National Administration of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
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13
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Han Q, Du L, Zhu L, Yu D. Review of the Application of Dual Drug Delivery Nanotheranostic Agents in the Diagnosis and Treatment of Liver Cancer. Molecules 2023; 28:7004. [PMID: 37894483 PMCID: PMC10608862 DOI: 10.3390/molecules28207004] [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: 08/15/2023] [Revised: 09/16/2023] [Accepted: 09/29/2023] [Indexed: 10/29/2023] Open
Abstract
Liver cancer has high incidence and mortality rates and its treatment generally requires the use of a combination treatment strategy. Therefore, the early detection and diagnosis of liver cancer is crucial to achieving the best treatment effect. In addition, it is imperative to explore multimodal combination therapy for liver cancer treatment and the synergistic effect of two liver cancer treatment drugs while preventing drug resistance and drug side effects to maximize the achievable therapeutic effect. Gold nanoparticles are used widely in applications related to optical imaging, CT imaging, MRI imaging, biomarkers, targeted drug therapy, etc., and serve as an advanced platform for integrated application in the nano-diagnosis and treatment of diseases. Dual-drug-delivery nano-diagnostic and therapeutic agents have drawn great interest in current times. Therefore, the present report aims to review the effectiveness of dual-drug-delivery nano-diagnostic and therapeutic agents in the field of anti-tumor therapy from the particular perspective of liver cancer diagnosis and treatment.
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Affiliation(s)
- Qinghe Han
- Radiology Department, The Second Affiliated Hospital of Jilin University, Changchun 130062, China; (Q.H.); (L.D.); (L.Z.)
| | - Lianze Du
- Radiology Department, The Second Affiliated Hospital of Jilin University, Changchun 130062, China; (Q.H.); (L.D.); (L.Z.)
| | - Lili Zhu
- Radiology Department, The Second Affiliated Hospital of Jilin University, Changchun 130062, China; (Q.H.); (L.D.); (L.Z.)
| | - Duo Yu
- Department of Radiotherapy, The Second Affiliated Hospital of Jilin University, Changchun 130062, China
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14
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Aly S, El-Kamel AH, Sheta E, El-Habashy SE. Chondroitin/Lactoferrin-dual functionalized pterostilbene-solid lipid nanoparticles as targeted breast cancer therapy. Int J Pharm 2023; 642:123163. [PMID: 37353100 DOI: 10.1016/j.ijpharm.2023.123163] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Revised: 06/01/2023] [Accepted: 06/19/2023] [Indexed: 06/25/2023]
Abstract
Breast cancer remains the leading cause of cancer-associated mortality in women. Research investigating novel therapeutic approaches is thus crucial, including phytotherapeutics. Pterostilbene (PTS) is a phytochemical agent with promising efficacy against breast cancer. Poor solubility, low bioavailability and chemical instability are major drawbacks compromising PTS functionality. Herein, novel PTS-loaded solid lipid nanoparticles (PTS-SLNs) were fabricated using the ultrasonication technique. Dual-functionalization with lactoferrin (Lf) and chondroitin-sulfate (CS; CS/Lf/PTS-SLNs) was adopted as active-targeting approach. CS/Lf/PTS-SLNs demonstrated nanoparticle-size (223.42 ± 18.71 nm), low PDI (0.33 ± 0.017), acceptable zeta potential (-11.85 ± 0.07 mV) and controlled release (72.93 ± 2.93% after 24 h). In vitro studies on triple-negative MDA-MB-231 revealed prominent cytotoxicity of CS/Lf/PTS-SLNs (2.63-fold IC50 reduction), higher anti-migratory effect and cellular uptake relative to PTS-solution. The in vivo anti-tumor efficacy in an orthotopic cancer model verified the superiority of CS/Lf/PTS-SLNs; achieving 2.4-fold decrease in tumor growth compared to PTS-solution. On the molecular level, CS/Lf/PTS-SLNs enhanced suppression of VEGF, down-regulated cyclin D1 and upregulated caspase-3 and BAX, compared to PTS-solution. Also, immunohistochemical assay confirmed the higher anti-tumorigenic effect of CS/Lf/PTS-SLNs (5.87-fold decrease in Bcl-2 expression) compared to PTS-solution. Our findings highlight CS/Lf/PTS-SLNs as a promising nanoplatform for phytotherapeutic targeted-breast cancer therapy.
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Affiliation(s)
- Sara Aly
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
| | - Amal H El-Kamel
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
| | - Eman Sheta
- Pathology Department, Faculty of Medicine, Alexandria University, Alexandria 21131, Egypt
| | - Salma E El-Habashy
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt
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15
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Qi N, Duan W, Gao D, Ma N, Zhang J, Feng J, Li A. "Guide" of muscone modification enhanced brain-targeting efficacy and anti-glioma effect of lactoferrin modified DTX liposomes. Bioeng Transl Med 2023; 8:e10393. [PMID: 36925685 PMCID: PMC10013770 DOI: 10.1002/btm2.10393] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 05/10/2022] [Accepted: 06/07/2022] [Indexed: 11/10/2022] Open
Abstract
Glioma is one of the most aggressive malignant diseases for human health. It is difficult to resect completely due to their invasiveness. The targeted delivery, as a noninvasive approach, is a major strategy for the development of treatments for brain tumors. Lactoferrin (Lf) receptors are over-expressed in both brain endothelial cells and glioma cells. Macromolecular Lf modified nanoparticles have been shown to enhance the brain targeting. Muscone is a "guide" drug that have been demonstrated to promote liposomes into the brain by modification. To further enhance the brain-targeting efficacy of Lf modified carriers, we designed that Lf and muscone dual-modified liposomes cross blood-brain barrier (BBB) and target to brain for enhanced docetaxel (DTX) brain delivery. The results showed that we successfully prepared Lf and muscone dual-modified liposomes (Lf-LP-Mu-DTX), the number of Lf molecules connected to the surface of per liposome was 28. Lf-LP-Mu-DTX increased uptake in both U87-MG cells and hCMEC/D3 cells, enhanced penetration of U87-MG tumor spheroid and in vitro BBB model, had better in vitro and in vivo anti-tumor effects. In conclusion, "guide" of muscone modification enhanced brain-targeting efficacy of Lf modified liposomes, Lf and muscone dual-modified docetaxel loaded liposomes present a potential brain-targeting drug delivery system for use in the future treatment of gliomas.
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Affiliation(s)
- Na Qi
- Cancer Center, Integrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhouChina
- Department of PharmacyGuilin Medical UniversityGuilinChina
| | - Wenjuan Duan
- Department of PharmacyGuilin Medical UniversityGuilinChina
- Department of PharmacyAffiliated Hospital of Jinggangshan UniversityChina
| | - Duan Gao
- Department of PharmacyGuilin Medical UniversityGuilinChina
| | - Ningzhu Ma
- Department of PharmacyGuilin Medical UniversityGuilinChina
| | - Jianguo Zhang
- Department of PharmacyGuilin Medical UniversityGuilinChina
| | - Jianfang Feng
- Department of PharmacyGuangxi University of Chinese MedicineNanningChina
| | - Aimin Li
- Cancer Center, Integrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhouChina
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16
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Proteins and their functionalization for finding therapeutic avenues in cancer: Current status and future prospective. Biochim Biophys Acta Rev Cancer 2023; 1878:188862. [PMID: 36791920 DOI: 10.1016/j.bbcan.2023.188862] [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: 06/24/2022] [Revised: 01/13/2023] [Accepted: 01/13/2023] [Indexed: 02/15/2023]
Abstract
Despite the remarkable advancement in the health care sector, cancer remains the second most fatal disease globally. The existing conventional cancer treatments primarily include chemotherapy, which has been associated with little to severe side effects, and radiotherapy, which is usually expensive. To overcome these problems, target-specific nanocarriers have been explored for delivering chemo drugs. However, recent reports on using a few proteins having anticancer activity and further use of them as drug carriers have generated tremendous attention for furthering the research towards cancer therapy. Biomolecules, especially proteins, have emerged as suitable alternatives in cancer treatment due to multiple favourable properties including biocompatibility, biodegradability, and structural flexibility for easy surface functionalization. Several in vitro and in vivo studies have reported that various proteins derived from animal, plant, and bacterial species, demonstrated strong cytotoxic and antiproliferative properties against malignant cells in native and their different structural conformations. Moreover, surface tunable properties of these proteins help to bind a range of anticancer drugs and target ligands, thus making them efficient delivery agents in cancer therapy. Here, we discuss various proteins obtained from common exogenous sources and how they transform into effective anticancer agents. We also comprehensively discuss the tumor-killing mechanisms of different dietary proteins such as bovine α-lactalbumin, hen egg-white lysozyme, and their conjugates. We also articulate how protein nanostructures can be used as carriers for delivering cancer drugs and theranostics, and strategies to be adopted for improving their in vivo delivery and targeting. We further discuss the FDA-approved protein-based anticancer formulations along with those in different phases of clinical trials.
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17
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Sethi G, Rath P, Chauhan A, Ranjan A, Choudhary R, Ramniwas S, Sak K, Aggarwal D, Rani I, Tuli HS. Apoptotic Mechanisms of Quercetin in Liver Cancer: Recent Trends and Advancements. Pharmaceutics 2023; 15:712. [PMID: 36840034 PMCID: PMC9960374 DOI: 10.3390/pharmaceutics15020712] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2023] [Revised: 02/13/2023] [Accepted: 02/16/2023] [Indexed: 02/23/2023] Open
Abstract
Due to rising incidence rates of liver cancer and worries about the toxicity of current chemotherapeutic medicines, the hunt for further alternative methods to treat this malignancy has escalated. Compared to chemotherapy, quercetin, a flavonoid, is relatively less harmful to normal cells and is regarded as an excellent free-radical scavenger. Apoptotic cell death of cancer cells caused by quercetin has been demonstrated by many prior studies. It is present in many fruits, vegetables, and herbs. Quercetin targets apoptosis, by upregulating Bax, caspase-3, and p21 while downregulating Akt, PLK-1, cyclin-B1, cyclin-A, CDC-2, CDK-2, and Bcl-2. Additionally, it has been reported to increase STAT3 protein degradation in liver cancer cells while decreasing STAT3 activation. Quercetin has a potential future in chemoprevention, based on substantial research on its anticancer effects. The current review discusses quercetin's mechanisms of action, nanodelivery strategies, and other potential cellular effects in liver cancer.
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Affiliation(s)
- Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore
| | - Prangya Rath
- Amity Institute of Environmental Sciences, Amity University, Noida 201303, India
| | - Abhishek Chauhan
- Amity Institute of Environmental Toxicology, Safety and Management, Amity University, Noida 201303, India
| | - Anuj Ranjan
- Academy of Biology and Biotechnology, Southern Federal University, 344090 Rostov-on-Don, Russia
| | - Renuka Choudhary
- Department of Biotechnology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, India
| | - Seema Ramniwas
- University Centre for Research and Development, University Institute of Pharmaceutical Sciences, Chandigarh University, Gharuan, Mohali 140413, India
| | | | - Diwakar Aggarwal
- Department of Biotechnology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, India
| | - Isha Rani
- Department of Biochemistry, Maharishi Markandeshwar College of Medical Sciences and Research (MMCMSR), Sadopur, Ambala 134007, India
| | - Hardeep Singh Tuli
- Department of Biotechnology, Maharishi Markandeshwar Engineering College, Maharishi Markandeshwar (Deemed to be University), Mullana, Ambala 133207, India
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18
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Jiang Z, Dai C. Potential Treatment Strategies for Hepatocellular Carcinoma Cell Sensitization to Sorafenib. J Hepatocell Carcinoma 2023; 10:257-266. [PMID: 36815094 PMCID: PMC9939808 DOI: 10.2147/jhc.s396231] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Accepted: 01/23/2023] [Indexed: 02/17/2023] Open
Abstract
Liver cancer is highly malignant, has a low sensitivity to chemotherapy, and is associated with poor patient prognosis. The last 3 years have seen the emergence of promising targeted therapies for the treatment of hepatocellular carcinoma (HCC). For over 10 years, before the discovery of lenvatinib, sorafenib was only first-line therapeutic agent available for the treatment of advanced HCC. However, several clinical studies have shown that a considerable proportion liver cancer patients are insensitive to sorafenib. Very few patients actually substantially benefit from treatment with sorafenib, and the overall efficacy of the drug has not been satisfactory; therefore, sorafenib has attracted considerable research attention. This study, which is based on previous studies and reports, reviews the potential mechanisms underlying sorafenib resistance and summarizes combination therapies and potential drugs that can be used to sensitize HCC cells to sorafenib.
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Affiliation(s)
- Zhonghao Jiang
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
| | - Chaoliu Dai
- Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China,Correspondence: Chaoliu Dai, Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China, Email
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19
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Zhang L, Wang M, Wu F, Liu L, Ren X, Hai Z. Intracellular Formation of Hemicyanine Nanoparticle Enhances Tumor-Targeting Photoacoustic Imaging and Photothermal Therapy. Adv Healthc Mater 2022; 12:e2202676. [PMID: 36535275 DOI: 10.1002/adhm.202202676] [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: 10/17/2022] [Revised: 12/08/2022] [Indexed: 12/24/2022]
Abstract
Alkaline phosphatase (ALP) is a tumor marker for early diagnosis and treatment. Tumor targeting can recognize and fight tumor cells more accurately from healthy cells. Glycyrrhetinic acid (GA) is a targeting ligand of liver tumors. Photoacoustic imaging (PAI) and photothermal therapy (PTT) are promising techniques for tumor diagnosis and treatment. The outstanding characteristics of Hemicyanine (HCy) dye make it suitable for tumor diagnosis and treatment. However, using HCy nanoparticle (HCy NP) for liver tumor-targeting PAI and PTT has not been reported. Herein, Probe-1 is developed to enhance PAI and PTT of liver tumors due to GA targeting and intracellular ALP-instructed self-assembly of HCy NP. Compared to Probe-2 without self-assembly ability, Probe-1 displays a 4.6-fold higher PAI signal or 1.7-fold lower half inhibitory concentrations in HepG2 cells. Moreover, Probe-1 shows extended retention time (10 vs 6 h) and 2.1-fold higher PAI signal than Probe-2 in HepG2 tumors. The HepG2 tumors in Group Probe-1 obviously increase 18 °C (Tmax : 55 °C) with a 3.3-fold decreased volume while that in Group Probe-2 mildly increase 9.8 °C (Tmax : 46.8 °C) with a 4.3-fold increased volume. It is envisioned that this smart self-assembly strategy can be easily adjusted for PAI and PTT of more tumors.
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Affiliation(s)
- Lele Zhang
- Key Laboratory of Structure and Functional Regulation of Hybrid Materials, Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui, 230601, China
| | - Minghui Wang
- Key Laboratory of Structure and Functional Regulation of Hybrid Materials, Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui, 230601, China
| | - Fangzheng Wu
- Key Laboratory of Structure and Functional Regulation of Hybrid Materials, Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui, 230601, China
| | - Li Liu
- Key Laboratory of Structure and Functional Regulation of Hybrid Materials, Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui, 230601, China
| | - Xingxing Ren
- Department of Gastroenterology, Third Affiliated Hospital of Guangzhou Medical University Guangzhou, Guangzhou, 510145, China
| | - Zijuan Hai
- Key Laboratory of Structure and Functional Regulation of Hybrid Materials, Ministry of Education, Institutes of Physical Science and Information Technology, Anhui University, Hefei, Anhui, 230601, China
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20
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Kharouba M, El-Kamel A, Mehanna R, Thabet E, Heikal L. Pitavastatin-loaded bilosomes for oral treatment of hepatocellular carcinoma: a repurposing approach. Drug Deliv 2022; 29:2925-2944. [PMID: 36081339 PMCID: PMC9467608 DOI: 10.1080/10717544.2022.2120925] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2022] [Revised: 08/29/2022] [Accepted: 08/29/2022] [Indexed: 11/05/2022] Open
Abstract
Albeit its established efficacy as an anti-hyperlipidemic agent, pitavastatin (PIT) has been shown to have other various therapeutic effects. One of these effects is the anti-cancer activity against hepatocellular carcinoma (HCC). This effect has been evaluated in this study for the first time via its oral delivery loaded in bilosomes both in vitro in hepatocellular carcinoma (HCC) cell line; HepG2 and in vivo in an Ehrlich ascites carcinoma (EAC) model. Moreover, the impact of surface modification of bilosomes with lactoferrin (LF) as an active targeting ligand for HCC was investigated. Bilosomes were prepared by thin-film hydration and different molar phospholipid to bile salt ratios were used to optimize the bilosomal formulation. The molar phospholipid to bile salt ratio was adjusted to 4:1 at pH 7.4. LF-coated bilosomes possessed a particle size, PDI, entrapment efficiency, and zeta potential of 112.28 nm ± 6.35, 0.229 ± 0.06, 90.56% ± 3.22, and -7.86 mV ± 1.13, respectively. LF-coated bilosomes also increased permeation of PIT when tested on Caco-2 cells by 3.1-folds (compared to uncoated ones or free PIT solution). It also improved the cytotoxicity of HepG2 spheroids 44-folds more than PIT-free solution. RT-PCR analysis showed that LF-coated PIT-loaded bilosomes caused an improvement (2-fold increase) in the apoptotic potential of PIT mediated by caspase-3. In conclusion, the optimized LF-coated PIT-loaded bilosomes were cytotoxic to HCC with improved hepatocytes permeation and cellular uptake. Thus, the proposed formula could be a promising treatment for HCC.
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Affiliation(s)
- Maged Kharouba
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Amal El-Kamel
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Radwa Mehanna
- Medical Physiology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- Center of Excellence for Research in Regenerative Medicine and its Applications CERRMA, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Eman Thabet
- Medical Physiology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt
- Center of Excellence for Research in Regenerative Medicine and its Applications CERRMA, Faculty of Medicine, Alexandria University, Alexandria, Egypt
| | - Lamia Heikal
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
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21
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Gautam AK, Kumar P, Maity B, Routholla G, Ghosh B, Chidambaram K, Begum MY, Al Fatease A, Rajinikanth P, Singh S, Saha S, M. R. V. Synthesis and appraisal of dalbergin-loaded PLGA nanoparticles modified with galactose against hepatocellular carcinoma: In-vitro, pharmacokinetic, and in-silico studies. Front Pharmacol 2022; 13:1021867. [PMID: 36386226 PMCID: PMC9650263 DOI: 10.3389/fphar.2022.1021867] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 10/11/2022] [Indexed: 07/02/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a common malignancy which affects a substantial number of individuals all over the globe. It is the third primary cause of death among persons with neoplasm and has the fifth largest mortality rate among men and the seventh highest mortality rate among women. Dalbergin (DL) is described to be effective in breast cancer via changing mRNA levels of apoptosis-related proteins. DL belongs to neoflavonoids, a drug category with low solubility and poor bioavailability. We created a synthetic version of this naturally occurring chemical, DL, and then analyzed it using 1H-NMR, 13C-NMR, and LC-MS. We also made PLGA nanoparticles and then coated them with galactose. The design of experiment software was used to optimize DL-loaded galactose-modified PLGA nanoparticles. The optimized DL-nanoformulations (DLF) and DL-modified nanoformulations (DLMF) were analyzed for particle size, polydispersity index, shape, and potential interactions. In-vitro experiments on liver cancer cell lines (HepG2) are used to validate the anti-proliferative efficacy of the modified DLMF. The in-vitro research on HepG2 cell lines also demonstrated cellular accumulation of DLF and DLMF by FITC level. The in-vitro result suggested that DLMF has high therapeutic effectiveness against HCC. In-vivo pharmacokinetics and bio-distribution experiments revealed that DLMF excelled pristine DL in terms of pharmacokinetic performance and targeted delivery, which is related to galactose's targeting activity on the asialoglycoprotein receptor (ASGPR) in hepatic cells. Additionally, we performed an in-silico study of DL on caspase 3 and 9 proteins, and the results were found to be -6.7 kcal/mol and -6.6 kcal/mol, respectively. Our in-silico analysis revealed that the DL had strong apoptotic properties against HCC.
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Affiliation(s)
- Anurag Kumar Gautam
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India
| | - Pranesh Kumar
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India
- Department of Pharmacology, Aryakul College of Pharmacy & Research, Lucknow, Uttar Pradesh, India
| | - Biswanath Maity
- Centre of Biomedical Research, SGPGIMS Campus, Lucknow, Uttar Pradesh, India
| | - Ganesh Routholla
- Department of Pharmacy, BITS-Pilani Hyderabad Campus Hyderabad, Hyderabad, India
| | - Balaram Ghosh
- Department of Pharmacy, BITS-Pilani Hyderabad Campus Hyderabad, Hyderabad, India
| | - Kumarappan Chidambaram
- Department of Pharmacology and Toxicology, School of Pharmacy, King Khalid University, Abha, Saudi Arabia
| | - M. Yasmin Begum
- Department of Pharmaceutics, King Khalid University, Abha, Saudi Arabia
| | - Adel Al Fatease
- Department of Pharmaceutics, King Khalid University, Abha, Saudi Arabia
| | - P.S. Rajinikanth
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India
| | - Sanjay Singh
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India
| | - Sudipta Saha
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India
| | - Vijayakumar M. R.
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, India
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22
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Li Z, Deng H, Guo X, Yan S, Lu C, Zhao Z, Feng X, Li Q, Wang J, Zeng J, Ma X. Effective dose/duration of natural flavonoid quercetin for treatment of diabetic nephropathy: A systematic review and meta-analysis of rodent data. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 105:154348. [PMID: 35908521 DOI: 10.1016/j.phymed.2022.154348] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 06/29/2022] [Accepted: 07/17/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Given the challenges on diabetic nephropathy (DN) treatment, research has been carried out progressively focusing on dietary nutrition and natural products as a novel option with the objective of enhancing curative effect and avoiding adverse reactions. As a representative, Quercetin (Qu) has proved to be of great value in current data. PURPOSE We aimed to synthetize the evidence regarding the therapeutic effect and specific mechanism of quercetin on DN via systematically reviewing and performing meta-analysis. METHODS Preclinical literature published prior to August 2021, was systematical retrieval and manually filtrated across four major databases including PubMed, Web of Science, EMBASE and Cochrane library. Pooled overall effect sizes of results were generated by STATA 16.0, and underlying mechanisms were summarized. Three-dimensional dose/time-effect analyses and radar maps were conducted to examine the dosage/time-response relations between Qu and DN. RESULTS This paper pools all current available evidence in a comprehensive way, and shows the therapeutic benefits as well as potential action mechanisms of Qu in protecting the kidney against damage. A total of 304 potentially relevant citations were identified, of which 18 studies were enrolled into analysis. Methodological quality was calculated, resulting in an average score of 7.06/10. This paper provided the preliminary evidence that consumption of Qu could induce a statistical reduction in mesangial index, Scr, BUN, 24-h urinary protein, serum urea, BG, kidney index, TC, TG, LDL-C, AST, MDA, AGE, TNF-α, TGF-β1, TGF-β1 mRNA, CTGF and IL-1β, whereas HDL-C, SOD, GSH, GSH-Px, CAT and smad-7 were significantly increased. Furthermore, Qu could remarkably improve the renal pathology. In terms of the mechanisms underlying therapy of DN, Qu exerts anti-diabetic nephropathy properties possibly through PI3K/PKB, AMPK-P38 MAPK, SCAP/SREBP2/LDLr, mtROS-TRX/TXNIP/NLRP3/IL-1β, TGF-β1/Smad, Nrf2/HO-1, Hippo, mTORC1/p70S6K and SHH pathways. Dose/time-response images predicted a modest association between Qu dosage consumption/administration length and therapeutic efficacy, with the optimal dosage at 90-150 mg/kg/d and administration length ranging from 8 weeks to 12 weeks. CONCLUSIONS Quercetin exhibit highly pleiotropic actions, which simultaneously contributes to prevent fundamental progression of DN, such as hyperglycemia, dyslipidemia, inflammation, fibrotic lesions and oxidative stress. The therapeutic effect becomes stronger when Qu administration at higher dosages lasts for longer durations. Taken together, quercetin could be used in patients with DN as a promising agent, which has well-established safety profiles and nontoxicity according to existing literature.
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Affiliation(s)
- Ziyu Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Haichuan Deng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Xiaochuan Guo
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Sining Yan
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Chaorui Lu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Zewei Zhao
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Xinyu Feng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Qihong Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Jiayi Wang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610075, China
| | - Jinhao Zeng
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
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Yan X, Li M, Xu X, Liu X, Liu F. Zein-based nano-delivery systems for encapsulation and protection of hydrophobic bioactives: A review. Front Nutr 2022; 9:999373. [PMID: 36245539 PMCID: PMC9554640 DOI: 10.3389/fnut.2022.999373] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Accepted: 08/25/2022] [Indexed: 12/25/2022] Open
Abstract
Zein is a kind of excellent carrier materials to construct nano-sized delivery systems for hydrophobic bioactives, owing to its unique interfacial behavior, such as self-assembly and packing into nanoparticles. In this article, the chemical basis and preparation methods of zein nanoparticles are firstly reviewed, including chemical crosslinking, emulsification/solvent evaporation, antisolvent, pH-driven method, etc., as well as the pros and cons of different preparation methods. Various strategies to improve their physicochemical properties are then summarized. Lastly, the encapsulation and protection effects of zein-based nano-sized delivery systems (e.g., nanoparticles, nanofibers, nanomicelles and nanogels) are discussed, using curcumin as a model bioactive ingredient. This review will provide guidance for the in-depth development of hydrophobic bioactives formulations and improve the application value of zein in the food industry.
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Affiliation(s)
- Xiaojia Yan
- College of Food Science and Engineering, Northwest A&F University, Xianyang, China
| | - Moting Li
- College of Food Science and Engineering, Northwest A&F University, Xianyang, China
| | - Xingfeng Xu
- College of Food Science and Engineering, Qingdao Agricultural University, Qingdao, China
| | - Xuebo Liu
- College of Food Science and Engineering, Northwest A&F University, Xianyang, China
| | - Fuguo Liu
- College of Food Science and Engineering, Northwest A&F University, Xianyang, China
- *Correspondence: Fuguo Liu
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24
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Tian H, Zhang T, Qin S, Huang Z, Zhou L, Shi J, Nice EC, Xie N, Huang C, Shen Z. Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies. J Hematol Oncol 2022; 15:132. [PMID: 36096856 PMCID: PMC9469622 DOI: 10.1186/s13045-022-01320-5] [Citation(s) in RCA: 159] [Impact Index Per Article: 53.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2022] [Accepted: 07/20/2022] [Indexed: 12/24/2022] Open
Abstract
Poor targeting of therapeutics leading to severe adverse effects on normal tissues is considered one of the obstacles in cancer therapy. To help overcome this, nanoscale drug delivery systems have provided an alternative avenue for improving the therapeutic potential of various agents and bioactive molecules through the enhanced permeability and retention (EPR) effect. Nanosystems with cancer-targeted ligands can achieve effective delivery to the tumor cells utilizing cell surface-specific receptors, the tumor vasculature and antigens with high accuracy and affinity. Additionally, stimuli-responsive nanoplatforms have also been considered as a promising and effective targeting strategy against tumors, as these nanoplatforms maintain their stealth feature under normal conditions, but upon homing in on cancerous lesions or their microenvironment, are responsive and release their cargoes. In this review, we comprehensively summarize the field of active targeting drug delivery systems and a number of stimuli-responsive release studies in the context of emerging nanoplatform development, and also discuss how this knowledge can contribute to further improvements in clinical practice.
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Affiliation(s)
- Hailong Tian
- Department of Otorhinolaryngology and Head and Neck Surgery, The Affiliated Lihuili Hospital, Ningbo University, 315040, Ningbo, Zhejiang, China.,State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China
| | - Tingting Zhang
- Department of Otorhinolaryngology and Head and Neck Surgery, The Affiliated Lihuili Hospital, Ningbo University, 315040, Ningbo, Zhejiang, China.,State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China
| | - Siyuan Qin
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China
| | - Zhao Huang
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China
| | - Li Zhou
- State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China
| | - Jiayan Shi
- Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, VIC, Australia
| | - Edouard C Nice
- West China School of Basic Medical Sciences and Forensic Medicine, Sichuan university, Chengdu, 610041, China
| | - Na Xie
- Department of Otorhinolaryngology and Head and Neck Surgery, The Affiliated Lihuili Hospital, Ningbo University, 315040, Ningbo, Zhejiang, China. .,State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China. .,West China School of Basic Medical Sciences and Forensic Medicine, Sichuan university, Chengdu, 610041, China.
| | - Canhua Huang
- Department of Otorhinolaryngology and Head and Neck Surgery, The Affiliated Lihuili Hospital, Ningbo University, 315040, Ningbo, Zhejiang, China. .,State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
| | - Zhisen Shen
- Department of Otorhinolaryngology and Head and Neck Surgery, The Affiliated Lihuili Hospital, Ningbo University, 315040, Ningbo, Zhejiang, China.
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25
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Nisha R, Kumar P, Kumar U, Mishra N, Maurya P, Singh P, Tabassum H, Alka, Singh S, Guleria A, Saraf SA. Assessment of hyaluronic acid-modified imatinib mesylate cubosomes through CD44 targeted drug delivery in NDEA-induced hepatic carcinoma. Int J Pharm 2022; 622:121848. [DOI: 10.1016/j.ijpharm.2022.121848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 05/17/2022] [Accepted: 05/18/2022] [Indexed: 12/24/2022]
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26
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Mirazimi SMA, Dashti F, Tobeiha M, Shahini A, Jafari R, Khoddami M, Sheida AH, EsnaAshari P, Aflatoonian AH, Elikaii F, Zakeri MS, Hamblin MR, Aghajani M, Bavarsadkarimi M, Mirzaei H. Application of Quercetin in the Treatment of Gastrointestinal Cancers. Front Pharmacol 2022; 13:860209. [PMID: 35462903 PMCID: PMC9019477 DOI: 10.3389/fphar.2022.860209] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Accepted: 03/02/2022] [Indexed: 02/06/2023] Open
Abstract
Many cellular signaling pathways contribute to the regulation of cell proliferation, division, motility, and apoptosis. Deregulation of these pathways contributes to tumor cell initiation and tumor progression. Lately, significant attention has been focused on the use of natural products as a promising strategy in cancer treatment. Quercetin is a natural flavonol compound widely present in commonly consumed foods. Quercetin has shown significant inhibitory effects on tumor progression via various mechanisms of action. These include stimulating cell cycle arrest or/and apoptosis as well as its antioxidant properties. Herein, we summarize the therapeutic effects of quercetin in gastrointestinal cancers (pancreatic, gastric, colorectal, esophageal, hepatocellular, and oral).
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Affiliation(s)
| | - Fatemeh Dashti
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran
| | - Mohammad Tobeiha
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Ali Shahini
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Raha Jafari
- Department of Medicine, Mashhad Medical Sciences Branch, Islamic Azad University, Mashhad, Iran
| | - Mehrad Khoddami
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
| | - Amir Hossein Sheida
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Parastoo EsnaAshari
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Amir Hossein Aflatoonian
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Fateme Elikaii
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Melika Sadat Zakeri
- School of Medicine, Kashan University of Medical Sciences, Kashan, Iran.,Student Research Committee, Kashan University of Medical Sciences, Kashan, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg, Doornfontein, South Africa
| | - Mohammad Aghajani
- Infectious Disease Research Center, School of Nursing and Midwifery, Kashan University of Medical Sciences, Kashan, Iran
| | - Minoodokht Bavarsadkarimi
- Clinical Research Development Center, Mahdiyeh Educational Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Iran
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27
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Mokhtar S, Khattab SN, Elkhodairy KA, Teleb M, Bekhit AA, Elzoghby AO, Sallam MA. Methotrexate-Lactoferrin Targeted Exemestane Cubosomes for Synergistic Breast Cancer Therapy. Front Chem 2022; 10:847573. [PMID: 35392419 PMCID: PMC8980280 DOI: 10.3389/fchem.2022.847573] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2022] [Accepted: 02/16/2022] [Indexed: 01/01/2023] Open
Abstract
While the treatment regimen of certain types of breast cancer involves a combination of hormonal therapy and chemotherapy, the outcomes are limited due to the difference in the pharmacokinetics of both treatment agents that hinders their simultaneous and selective delivery to the cancer cells. Herein, we report a hybrid carrier system for the simultaneous targeted delivery of aromatase inhibitor exemestane (EXE) and methotrexate (MTX). EXE was physically loaded within liquid crystalline nanoparticles (LCNPs), while MTX was chemically conjugated to lactoferrin (Lf) by carbodiimide reaction. The anionic EXE-loaded LCNPs were then coated by the cationic MTX–Lf conjugate via electrostatic interactions. The Lf-targeted dual drug-loaded LCNPs exhibited a particle size of 143.6 ± 3.24 nm with a polydispersity index of 0.180. It showed excellent drug loading with an EXE encapsulation efficiency of 95% and an MTX conjugation efficiency of 33.33%. EXE and MTX showed synergistic effect against the MCF-7 breast cancer cell line with a combination index (CI) of 0.342. Furthermore, the Lf-targeted dual drug-loaded LCNPs demonstrated superior synergistic cytotoxic activity with a combination index (CI) of 0.242 and a dose reduction index (DRI) of 34.14 and 4.7 for EXE and MTX, respectively. Cellular uptake studies demonstrated higher cellular uptake of Lf-targeted LCNPs into MCF-7 cancer cells than non-targeted LCNPs after 4 and 24 h. Collectively, the targeted dual drug-loaded LCNPs are a promising candidate offering combinational hormonal therapy/chemotherapy for breast cancer.
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Affiliation(s)
- Sarah Mokhtar
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
- Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Sherine N. Khattab
- Chemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
- *Correspondence: Sherine N. Khattab, , ; Ahmed O. Elzoghby,
| | - Kadria A. Elkhodairy
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
- Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Mohamed Teleb
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Adnan A. Bekhit
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
- Pharmacy Program, Allied Health Department, College of Health and Sport Sciences, University of Bahrain, Al-Manamah, Bahrain
| | - Ahmed O. Elzoghby
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
- Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
- *Correspondence: Sherine N. Khattab, , ; Ahmed O. Elzoghby,
| | - Marwa A. Sallam
- Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
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Zhao X, Deng Y, Xue X, Liao L, Zhou M, Peng C, Li Y. Research Progress of Quercetin Delivery Systems. Curr Pharm Des 2022; 28:727-742. [PMID: 35301946 DOI: 10.2174/1381612828666220317141923] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 01/17/2022] [Indexed: 11/22/2022]
Abstract
Quercetin is the main dietary flavonoid with a wide range of pharmacological activities. However, the poor gastrointestinal absorption and low bioavailability of quercetin curtails its clinical applications.. Enhancement the bioavailability of quercetin focuses on the application of delivery systems technologies such as microparticle delivery systems, solid dispersions, encapsulation, phospholipid complexes, and hydrogels , which have been systematically reviewed .And theirapplications in vitro and in vivo animal experiments also been described, promoting the development and optimization of drug delivery system for clinical applications.
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Affiliation(s)
- Xingtao Zhao
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, Chengdu 611137, China
- National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources
| | - Ying Deng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, Chengdu 611137, China
- National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources
| | - Xinyan Xue
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, Chengdu 611137, China
- National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources
| | - Li Liao
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, Chengdu 611137, China
- National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources
| | - Mengting Zhou
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, Chengdu 611137, China
- National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources
| | - Cheng Peng
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, Chengdu 611137, China
- National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources
| | - Yunxia Li
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
- Key Laboratory of Standardization for Chinese Herbal Medicine, Ministry of Education, Chengdu 611137, China
- National Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources
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Teixeira S, Carvalho MA, Castanheira EMS. Functionalized Liposome and Albumin-Based Systems as Carriers for Poorly Water-Soluble Anticancer Drugs: An Updated Review. Biomedicines 2022; 10:486. [PMID: 35203695 PMCID: PMC8962385 DOI: 10.3390/biomedicines10020486] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/08/2022] [Accepted: 02/14/2022] [Indexed: 12/12/2022] Open
Abstract
Cancer is one of the leading causes of death worldwide. In the available treatments, chemotherapy is one of the most used, but has several associated problems, namely the high toxicity to normal cells and the resistance acquired by cancer cells to the therapeutic agents. The scientific community has been battling against this disease, developing new strategies and new potential chemotherapeutic agents. However, new drugs often exhibit poor solubility in water, which led researchers to develop functionalized nanosystems to carry and, specifically deliver, the drugs to cancer cells, targeting overexpressed receptors, proteins, and organelles. Thus, this review is focused on the recent developments of functionalized nanosystems used to carry poorly water-soluble drugs, with special emphasis on liposomes and albumin-based nanosystems, two major classes of organic nanocarriers with formulations already approved by the U.S. Food and Drug Administration (FDA) for cancer therapeutics.
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Affiliation(s)
- Sofia Teixeira
- Centre of Chemistry, Campus de Gualtar, University of Minho (CQUM), 4710-057 Braga, Portugal; (S.T.); (M.A.C.)
- Centre of Physics of Minho and Porto Universities (CF-UM-UP), Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal
| | - Maria Alice Carvalho
- Centre of Chemistry, Campus de Gualtar, University of Minho (CQUM), 4710-057 Braga, Portugal; (S.T.); (M.A.C.)
| | - Elisabete M. S. Castanheira
- Centre of Physics of Minho and Porto Universities (CF-UM-UP), Campus de Gualtar, University of Minho, 4710-057 Braga, Portugal
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30
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Zhou L, Li Y, Liang Q, Liu J, Liu Y. Combination therapy based on targeted nano drug co-delivery systems for liver fibrosis treatment: A review. J Drug Target 2022; 30:577-588. [PMID: 35179094 DOI: 10.1080/1061186x.2022.2044485] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Liver fibrosis is the hallmark of liver disease and occurs prior to the stages of cirrhosis and hepatocellular carcinoma. Any type of liver damage or inflammation can result in fibrosis. Fibrosis does not develop overnight, but rather as a result of the long-term action of injury factors. At present, however, there are no good treatment methods or specific drugs other than removing the pathogenic factors. Drug application is still limited, which means that drugs with good performance in vitro cannot achieve good therapeutic effects in vivo, owing to various factors such as poor drug targeting, large side effects, and strong hydrophobicity. Hepatic stellate cells (HSC) are the primary effector cells in liver fibrosis. The nano-drug delivery system is a new and safe drug delivery system that has many advantages which are widely used in the field of liver fibrosis. Drug resistance and side effects can be reduced when two or more drugs are used in combination drug delivery. Combination therapy of drugs with different targets has emerged as a novel approach to treating liver fibrosis, and the nano co-delivery system enhances the benefits of combination therapy. While nano co-delivery systems can maximize benefits while avoiding drug side effects, this is precisely the advantage of the nano co-delivery system. This review briefly described the pathogenesis and current treatment strategies, the different co-delivery systems of combination drugs in the nano delivery system, and targeting strategies for nano delivery systems on liver fibrosis therapy. Because of their superior performance, nano delivery systems and targeting drug delivery systems have received a lot of attention in the new drug delivery system. The new delivery systems offer a new pathway in the treatment of liver fibrosis, and it is believed that it can be a new treatment for fibrosis in the future. Nano co-delivery system of combination drugs and targeting strategies has proven the effectiveness of anti-fibrosis at the experimental level.
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Affiliation(s)
- Liyue Zhou
- Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Yifan Li
- Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Qiangwei Liang
- Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Jinxia Liu
- Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, China
| | - Yanhua Liu
- Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, Yinchuan, China.,Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, China
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Abad I, Conesa C, Sánchez L. Development of Encapsulation Strategies and Composite Edible Films to Maintain Lactoferrin Bioactivity: A Review. MATERIALS 2021; 14:ma14237358. [PMID: 34885510 PMCID: PMC8658689 DOI: 10.3390/ma14237358] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/30/2021] [Revised: 11/23/2021] [Accepted: 11/23/2021] [Indexed: 12/15/2022]
Abstract
Lactoferrin (LF) is a whey protein with various and valuable biological activities. For this reason, LF has been used as a supplement in formula milk and functional products. However, it must be considered that the properties of LF can be affected by technological treatments and gastrointestinal conditions. In this article, we have revised the literature published on the research done during the last decades on the development of various technologies, such as encapsulation or composite materials, to protect LF and avoid its degradation. Multiple compounds can be used to conduct this protective function, such as proteins, including those from milk, or polysaccharides, like alginate or chitosan. Furthermore, LF can be used as a component in complexes, nanoparticles, hydrogels and emulsions, to encapsulate, protect and deliver other bioactive compounds, such as essential oils or probiotics. Additionally, LF can be part of systems to deliver drugs or to apply certain therapies to target cells expressing LF receptors. These systems also allow improving the detection of gliomas and have also been used for treating some pathologies, such as different types of tumours. Finally, the application of LF in edible and active films can be effective against some contaminants and limit the increase of the natural microbiota present in meat, for example, becoming one of the most interesting research topics in food technology.
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Affiliation(s)
- Inés Abad
- Departamento de Producción Animal y Ciencia de los Alimentos, Facultad de Veterinaria, Universidad de Zaragoza, 50013 Zaragoza, Spain; (I.A.); (C.C.)
- Instituto Agroalimentario de Aragón (IA2), Universidad de Zaragoza-CITA, 50013 Zaragoza, Spain
| | - Celia Conesa
- Departamento de Producción Animal y Ciencia de los Alimentos, Facultad de Veterinaria, Universidad de Zaragoza, 50013 Zaragoza, Spain; (I.A.); (C.C.)
| | - Lourdes Sánchez
- Departamento de Producción Animal y Ciencia de los Alimentos, Facultad de Veterinaria, Universidad de Zaragoza, 50013 Zaragoza, Spain; (I.A.); (C.C.)
- Instituto Agroalimentario de Aragón (IA2), Universidad de Zaragoza-CITA, 50013 Zaragoza, Spain
- Correspondence: ; Tel.: +34-976-761-585
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Glycyrrhizic Acid and Its Hydrolyzed Metabolite 18β-Glycyrrhetinic Acid as Specific Ligands for Targeting Nanosystems in the Treatment of Liver Cancer. Pharmaceutics 2021; 13:pharmaceutics13111792. [PMID: 34834206 PMCID: PMC8621092 DOI: 10.3390/pharmaceutics13111792] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2021] [Revised: 09/28/2021] [Accepted: 10/19/2021] [Indexed: 01/10/2023] Open
Abstract
Glycyrrhizic acid and its hydrolyzed metabolite 18β-glycyrrhetinic acid, obtained from the plant Glycyrrhiza glabra, have numerous pharmacological activities, such as anti-inflammatory, anti-ulcerative, antiallergic, immunomodulatory, antiviral, antitumor, hepatoprotective, and antioxidant effects, and others. In addition to the pharmacological activities, in the 1980s, an interaction and uptake of these molecules by the liver was verified, which was later confirmed by other studies through the discovery of specific receptors in the hepatocytes. The presence of these specific receptors in the liver led to vectorization and delivery of drugs, by the introduction of glycyrrhizic acid or glycyrrhetinic acid on the surface of nanosystems, for the treatment of liver diseases. This review describes experimental evidence of vectorization by conjugating glycyrrhizic acid or glycyrrhetinic acid to nanosystems and delivery of antitumor drugs for the treatment of liver cancer and also describes the techniques used to perform this conjugation. We have shown that due to the existence of specific receptors for these molecules, in addition to the targeting of nanosystems to hepatocytes, nanosystems having glycyrrhizic acid or glycyrrhetinic acid on their surface had the same therapeutic effect in a significantly lower dose compared to the free drug and unconjugated nanosystems, with consequent reduction of side effects and toxicity.
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Hafez DA, Hassanin IA, Teleb M, Khattab SN, Elkhodairy KA, Elzoghby AO. Recent advances in nanomedicine-based delivery of histone deacetylase inhibitors for cancer therapy. Nanomedicine (Lond) 2021; 16:2305-2325. [PMID: 34551585 DOI: 10.2217/nnm-2021-0196] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Histone deacetylase inhibitors (HDACi) are cancer therapeutics that operate at the epigenetic level and which have recently gained wide attention. However, the applications of HDACi are generally hindered by their poor physicochemical characteristics and unfavorable pharmacokinetic profile. Inspired by the approved nanomedicine-based drugs in the market, nanocarriers could provide a resort to circumvent the limitations imposed by HDACi. Enhanced tumor targeting, improved cellular uptake and reduced toxicity are major advantages offered by HDACi-loaded nanoparticles. More importantly, site-specific drug delivery can be achieved via engineered stimuli-responsive nanosystems. In this review we elucidate the anticancer mechanisms of HDACi and their structure-activity relationships, with a special focus on their nanomedicine-based delivery, different drug loading concepts and their implications.
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Affiliation(s)
- Dina A Hafez
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
| | - Islam A Hassanin
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Biotechnology, Institute of Graduate Studies & Research, Alexandria University, Alexandria, 21526, Egypt
| | - Mohamed Teleb
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
| | - Sherine N Khattab
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, 21321, Egypt
| | - Kadria A Elkhodairy
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
| | - Ahmed O Elzoghby
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
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Fawzi Kabil M, Nasr M, El-Sherbiny IM. Conventional and hybrid nanoparticulate systems for the treatment of hepatocellular carcinoma: An updated review. Eur J Pharm Biopharm 2021; 167:9-37. [PMID: 34271117 DOI: 10.1016/j.ejpb.2021.07.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 06/28/2021] [Accepted: 07/07/2021] [Indexed: 12/12/2022]
Abstract
Hepatocellular carcinoma (HCC) is considered a serious malignancy which affects a large number of people worldwide. Despite the presence of some diagnostic techniques for HCC, the fact that its symptoms somehow overlap with other diseases causes it to be diagnosed at a late stage, hence negatively affecting the prognosis of the disease. The currently available treatment strategies have many shortcomings such as high cost, induction of serious side effects as well as multiple drug resistance, hence resulting in therapeutic failure. Accordingly, nanoformulations have been developed in order to overcome the clinical challenges, enhance the therapeutic efficacy, and elicit chemotherapy tailor-ability. Hybrid nanoparticulate carriers in particular, which are composed of two or more drug vehicles with different physicochemical characteristics combined together in one system, have been recently reported to advance nanotechnology-based therapies. Therefore, this review sheds the light on HCC, and the role of nanotechnology and hybrid nanoparticulate carriers as well as the latest developments in the use of conventional nanoparticles in combating this disease.
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Affiliation(s)
- Mohamed Fawzi Kabil
- Center for Materials Science, University of Science and Technology, Zewail City of Science and Technology, 6th October City, Giza 12578, Egypt
| | - Maha Nasr
- Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Ibrahim M El-Sherbiny
- Center for Materials Science, University of Science and Technology, Zewail City of Science and Technology, 6th October City, Giza 12578, Egypt.
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35
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Li Z, Wang F, Li Y, Wang X, Lu Q, Wang D, Qi C, Li C, Li Z, Lian B, Tian G, Gao Z, Zhang B, Wu J. Combined anti-hepatocellular carcinoma therapy inhibit drug-resistance and metastasis via targeting "substance P-hepatic stellate cells-hepatocellular carcinoma" axis. Biomaterials 2021; 276:121003. [PMID: 34273686 DOI: 10.1016/j.biomaterials.2021.121003] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2021] [Revised: 06/21/2021] [Accepted: 07/01/2021] [Indexed: 12/13/2022]
Abstract
Peripheral nerves have emerged as the important components in tumor microenvironment (TME), which could activate hepatic stellate cells (HSCs) by secreting substance P (SP), leading to hepatocellular carcinoma (HCC) invasion and metastasis. Herein, we proposed a novel anti-HCC concept of blocking "SP-HSCs-HCC" axis for omnidirectional inhibition of HCC development. To pursue this aim, the novel CAP/GA-sHA-DOX NPs were developed for targeted co-delivery of capsaicin (CAP) and doxorubicin (DOX) using glycyrrhetinic acid (GA) modified sulfated-HA (sHA) as nanocarriers. Among that, CAP could inhibit the activation of HSCs as an inhibitor of SP. Notably, to real mimic "SP-HSCs-HCC" axis for in vitro and in vivo evaluation, both "SP + LX-2+BEL-7402" co-cultured cell model and "SP + m-HSC + H22" co-implantation mice model were attempted for the first time. Furthermore, in vivo anti-HCC effects were performed in three different tumor-bearing models: subcutaneous implantation of H22 or "SP + m-HSC + H22", intravenous injection of H22 for lung metastasis, and orthotopic implantation of H22 for primary HCC. Our results showed that CAP/GA-sHA-DOX NPs could be efficiently taken up by tumor cells and activated HSCs (aHSCs) simultaneously, and effectively inhibit tumor drug-resistance and migration by blocking SP-induced HSCs activation. In addition, CAP/GA-sHA-DOX NPs exhibited low ECM deposition, less tumor angiogenesis, and superior in vivo anti-HCC effects. The anti-HCC mechanisms revealed that CAP/GA-sHA-DOX NPs could down-regulate the expression level of Vimentin and P-gp, reverse epithelial-mesenchymal transition (EMT) of tumor cells. In brief, the nano-sized combination therapy based on GA-sHA-DOX polymers could effectively inhibit drug-resistance and metastasis of HCC by blocking "SP-HSCs-HCC" axis, which provides a promising approach for cancer therapy.
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Affiliation(s)
- Zhipeng Li
- School of Bioscience and Technology, Weifang Medical University, PR China
| | - Fangqing Wang
- School of Bioscience and Technology, Weifang Medical University, PR China
| | - Yanying Li
- School of Bioscience and Technology, Weifang Medical University, PR China
| | - Xiaoxue Wang
- School of Bioscience and Technology, Weifang Medical University, PR China
| | - Qiao Lu
- School of Bioscience and Technology, Weifang Medical University, PR China
| | - Di Wang
- School of Nursing, Weifang Medical University, PR China
| | - Cuiping Qi
- School of Nursing, Weifang Medical University, PR China
| | - Chenglei Li
- School of Pharmacy, Weifang Medical University, Weifang, 261053, PR China
| | - Zhaohuan Li
- School of Pharmacy, Weifang Medical University, Weifang, 261053, PR China
| | - Bo Lian
- School of Bioscience and Technology, Weifang Medical University, PR China
| | - Guixiang Tian
- School of Bioscience and Technology, Weifang Medical University, PR China
| | - Zhiqin Gao
- School of Bioscience and Technology, Weifang Medical University, PR China.
| | - Bo Zhang
- School of Pharmacy, Weifang Medical University, Weifang, 261053, PR China.
| | - Jingliang Wu
- School of Bioscience and Technology, Weifang Medical University, PR China.
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36
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AbdElhamid AS, Zayed DG, Heikal L, Khattab SN, Mady OY, El-Gizawy SA, Elzoghby AO. Recent advances in polymer shell oily-core nanocapsules for drug-delivery applications. Nanomedicine (Lond) 2021; 16:1613-1625. [PMID: 34189946 DOI: 10.2217/nnm-2021-0037] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Polymeric nanocapsules are vesicular drug-delivery systems composed of an inner oily reservoir surrounded by polymeric membranes. Nanocapsules have various advantages over other nanovesicular systems such as providing controlled drug release properties. We discuss the recent advances in polymeric shell oily-core nanocapsules, illustrating the different types of polymers used and their implementation. Nanocapsules can be utilized for many purposes, especially encapsulation of highly lipophilic drugs. They have been shown to have variable applications, especially in cancer therapy, due to the ability of the polymeric shell to direct the loaded drugs to their target sites, as well as their high internalization efficacy. Those productive applications guaranteed their high potential as drug-delivery systems. However, their clinical development is still in an early stage.
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Affiliation(s)
- Ahmed S AbdElhamid
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Dina G Zayed
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Lamia Heikal
- Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
| | - Sherine N Khattab
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, 21321, Egypt
| | - Omar Y Mady
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Sanaa A El-Gizawy
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Ahmed O Elzoghby
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.,Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
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Wang F, Li Y, Jiang H, Li C, Li Z, Qi C, Li Z, Gao Z, Zhang B, Wu J. Dual-Ligand-Modified Liposomes Co-Loaded with Anti-Angiogenic and Chemotherapeutic Drugs for Inhibiting Tumor Angiogenesis and Metastasis. Int J Nanomedicine 2021; 16:4001-4016. [PMID: 34135585 PMCID: PMC8200177 DOI: 10.2147/ijn.s309804] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Accepted: 05/17/2021] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Tumor angiogenesis has been proven to potentiate tumor growth and metastasis; therefore, the strategies targeting tumor-related angiogenesis have great potentials in antitumor therapy. METHODS Here, the GA&Gal dual-ligand-modified liposomes co-loaded with curcumin and combretastatin A-4 phosphate (CUCA/GA&Gal-Lip) were prepared and characterized. A novel "BEL-7402+HUVEC" co-cultured cell model was established to mimic tumor microenvironment. The cytotoxicity and migration assays were performed against the novel co-cultured model. Angiogenesis ability was evaluated by tube formation test, and in vivo metastatic ability was evaluated by lung metastasis test. RESULTS The result demonstrated that dual-ligand-modified liposomes showed greater inhibition of tumor angiogenesis and metastasis in comparison with other combined groups. Significantly, the mechanism analysis revealed that curcumin and combretastatin A-4 phosphate could inhibit tumor angiogenesis and metastasis via down-regulation of VEGF and VEGFR2 expression, respectively, and that GA&Gal-Lip could improve antitumor effect by GA/Gal-mediated active-targeting delivery. CONCLUSION CUCA/GA&Gal-Lip hold great potentials in hepatoma-targeting delivery of antitumor drugs and can achieve anti-angiogenic and anti-metastatic effects by simultaneously blocking VEGF/VEGFR2 signal pathway, therefore exhibiting superior anti-hepatoma efficacy.
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Affiliation(s)
- Fangqing Wang
- School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, People’s Republic of China
| | - Yanying Li
- School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, People’s Republic of China
| | - Hong Jiang
- School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, People’s Republic of China
| | - Chenglei Li
- School of Pharmacy, Weifang Medical University, Weifang, 261053, People’s Republic of China
| | - Zhaohuan Li
- School of Pharmacy, Weifang Medical University, Weifang, 261053, People’s Republic of China
| | - Cuiping Qi
- School of Nursing, Weifang Medical University, Weifang, 261053, People’s Republic of China
| | - Zhipeng Li
- School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, People’s Republic of China
| | - Zhiqin Gao
- School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, People’s Republic of China
| | - Bo Zhang
- School of Pharmacy, Weifang Medical University, Weifang, 261053, People’s Republic of China
| | - Jingliang Wu
- School of Bioscience and Technology, Weifang Medical University, Weifang, 261053, People’s Republic of China
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38
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Coroli A, Romano R, Saccani A, Raddadi N, Mele E, Mascia L. An In-Vitro Evaluation of the Characteristics of Zein-Based Films for the Release of Lactobionic Acid and the Effects of Oleic Acid. Polymers (Basel) 2021; 13:1826. [PMID: 34072945 PMCID: PMC8198277 DOI: 10.3390/polym13111826] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Revised: 05/21/2021] [Accepted: 05/28/2021] [Indexed: 11/17/2022] Open
Abstract
Lactobionic acid (LBA) is widely used in different industrial sectors owing to its biocompatibility characteristics as well as antioxidant and antimicrobial properties. In this study, mixtures of the protein zein with LBA and with the addition of oleic acid (OA) as a ternary system were investigated as drug delivery films for the release of LBA. The chosen combinations exploit the vast difference in water solubility between LBA and the other two components (zein and OA). DSC thermograms and dynamic mechanical spectra, alongside electron microscopy images, were used to describe the microstructural features of the films and were found to provide insights for the release of LBA from the two examined zein-based films immersed in an aqueous physiological solution. For both film systems, a burst release behavior was observed, followed by a rapid and total extraction of LBA. The required immersion time for the total extraction of LBA was greatly reduced when oleic acid was added to the precursor solution mixture for producing the films. The LBA released from the zein-based films was found to exhibit both the expected antioxidant properties as well as exerting bacteriostatic effects towards Escherichia coli and Staphylococcus epidermidis.
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Affiliation(s)
- Alessandro Coroli
- Department of Civil, Chemical, Environmental and Materials Engineering, University of Bologna, 40131 Bologna, Italy; (A.C.); (R.R.); (A.S.); (N.R.)
| | - Roberta Romano
- Department of Civil, Chemical, Environmental and Materials Engineering, University of Bologna, 40131 Bologna, Italy; (A.C.); (R.R.); (A.S.); (N.R.)
| | - Andrea Saccani
- Department of Civil, Chemical, Environmental and Materials Engineering, University of Bologna, 40131 Bologna, Italy; (A.C.); (R.R.); (A.S.); (N.R.)
| | - Noura Raddadi
- Department of Civil, Chemical, Environmental and Materials Engineering, University of Bologna, 40131 Bologna, Italy; (A.C.); (R.R.); (A.S.); (N.R.)
| | - Elisa Mele
- Materials Department, Loughborough University, Loughborough LE11 3TU, UK
| | - Leno Mascia
- Materials Department, Loughborough University, Loughborough LE11 3TU, UK
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A novel 'smart' PNIPAM-based copolymer for breast cancer targeted therapy: Synthesis, and characterization of dual pH/temperature-responsive lactoferrin-targeted PNIPAM-co-AA. Colloids Surf B Biointerfaces 2021; 202:111694. [PMID: 33740633 DOI: 10.1016/j.colsurfb.2021.111694] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 03/02/2021] [Accepted: 03/09/2021] [Indexed: 12/12/2022]
Abstract
Despite the active research towards introducing novel anticancer agents, the long-term sequelae and side effects of chemotherapy remain the major obstacle to achieving clinical success. Recent cancer research is now utilizing the medicinal chemistry toolbox to tailor novel 'smart' carrier systems that can reduce the major limitations of chemotherapy ranging from non-specificity and ubiquitous biodistribution to systemic toxicity. In this aspect, various stimuli-responsive polymers have gained considerable interest due to their intrinsic tumor targeting properties. Among these polymers, poly(N-isopropylacrylamide (PNIPAM) has been chemically modified to tune its thermoresponsivity or even copolymerized to endow new stimulus responsiveness for enhancing tumor targeting. Herein, we set our design rationale to impart additional active targeting entity to pH/temperature-responsive PNIPAM-based polymer for more efficient controlled payloads accumulation at the tumor through cellular internalization via synthesizing novel "super intelligent" lactoferrin conjugated PNIPAM-acrylic acid (LF-PNIPAM-co-AA) copolymer. The synthesized copolymer was physicochemically characterized and evaluated as a smart nanocarrier for targeting breast cancer. In this regard, Honokiol (HK) was utilized as a model anticancer drug and encapsulated in the nanoparticles to overcome its lipophilic nature and allow its parenteral administration, for achieving sustainable drug release with targeting action. Results showed that the developed HK-loaded LF-PNIPAM-co-AA nanohydrogels displayed high drug loading capacity reaching to 18.65 wt.% with excellent physical and serum stability. Moreover, the prepared HK-loaded nanohydrogels exhibited efficient in vitro and in vivo antitumor activities. In vivo, HK-loaded nanohydrogels demonstrated suppression of VEGF-1 and Ki-67 expression levels, besides inducing apoptosis through upregulating the expression level of active caspase-3 in breast cancer-bearing mice. Overall, the developed nanohydrogels (NGs) with pH and temperature responsivity provide a promising nanocarrier for anticancer treatment.
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40
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Nisha R, Kumar P, Kumar U, Mishra N, Maurya P, Singh S, Singh P, Guleria A, Saha S, Saraf SA. Fabrication of Imatinib Mesylate-Loaded Lactoferrin-Modified PEGylated Liquid Crystalline Nanoparticles for Mitochondrial-Dependent Apoptosis in Hepatocellular Carcinoma. Mol Pharm 2020; 18:1102-1120. [PMID: 33356314 DOI: 10.1021/acs.molpharmaceut.0c01024] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) is a major cause of concern as it has substantial morbidity associated with it. Previous reports have ascertained the antiproliferative activity of imatinib mesylate (IMS) against diverse types of carcinomas, but limited bioavailability has also been reported. The present study envisaged optimized IMS-loaded lactoferrin (LF)-modified PEGylated liquid crystalline nanoparticles (IMS-LF-LCNPs) for effective therapy of IMS to HCC via asialoglycoprotein receptor (ASGPR) targeting. Results displayed that IMS-LF-LCNPs presented an optimum particle size of 120.40 ± 2.75 nm, a zeta potential of +12.5 ± 0.23 mV, and 73.94 ± 2.69% release. High-resolution transmission electron microscopy and atomic force microscopy were used to confirm the surface architecture of IMS-LF-LCNPs. The results of cytotoxicity and 4,6-diamidino-2-phenylindole revealed that IMS-LF-LCNPs had the highest growth inhibition and significant apoptotic effects. Pharmacokinetics and biodistribution studies showed that IMS-LF-LCNPs have superior pharmacokinetic performance and targeted delivery compared to IMS-LCNPs and plain IMS, which was attributed to the targeting action of LF that targets the ASGPR in hepatic cells. Next, our in vivo experiment established that the HCC environment existed due to suppression of BAX, cyt c, BAD, e-NOS, and caspase (3 and 9) genes, which thus owed upstream expression of Bcl-xl, iNOS, and Bcl-2 genes. The excellent therapeutic potential of IMS-LF-LCNPs began the significant stimulation of caspase-mediated apoptotic signals accountable for its anti-HCC prospect. 1H nuclear magnetic resonance (serum) metabolomics revealed that IMS-LF-LCNPs are capable of regulating the disturbed levels of metabolites linked to HCC triggered through N-nitrosodiethylamine. Therefore, IMS-LF-LCNPs are a potentially effective formulation against HCC.
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Affiliation(s)
- Raquibun Nisha
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow 226025, India
| | - Pranesh Kumar
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow 226025, India
| | - Umesh Kumar
- Centre of Biomedical Research, SGPGIMS Campus, Raebareli Road, Lucknow 226014, Uttar Pradesh, India
| | - Nidhi Mishra
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow 226025, India
| | - Priyanka Maurya
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow 226025, India
| | - Samipta Singh
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow 226025, India
| | - Priya Singh
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow 226025, India
| | - Anupam Guleria
- Centre of Biomedical Research, SGPGIMS Campus, Raebareli Road, Lucknow 226014, Uttar Pradesh, India
| | - Sudipta Saha
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow 226025, India
| | - Shubhini A Saraf
- Department of Pharmaceutical Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raibareli Road, Lucknow 226025, India
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Kumar S, Fayaz F, Pottoo FH, Bajaj S, Manchanda S, Bansal H. Nanophytomedicine Based Novel Therapeutic Strategies in Liver Cancer. Curr Top Med Chem 2020; 20:1999-2024. [DOI: 10.2174/1568026619666191114113048] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Revised: 06/25/2020] [Accepted: 06/29/2020] [Indexed: 02/06/2023]
Abstract
Liver cancer is the fifth (6.3% of all cancers i.e., 548,000 cases/year) and ninth (2.8% of all
cancers i.e., 244,000 cases/year) most prevalent cancer worldwide in men and women, respectively. Although
multiple choices of therapies are offered for Hepatocellular Carcinoma (HCC) like liver resection
or transplant, radiofrequency ablation, transarterial chemoembolization, radioembolization, and systemic
targeted agent, by the time of diagnosis, most of the cases of HCC are in an advanced stage, which
renders therapies like liver transplant or resection and local ablation impractical; and targeted therapy
has its shortcomings like general toxicity, imprecise selectivity, several adversative reactions, and resistance
development. Therefore, novel drugs with specificity and selectivity are needed to provide the potential
therapeutic response. Various researches have shown the potential of phytomedicines in liver
cancer by modulating cell growth, invasion, metastasis, and apoptosis. However, their therapeutic potential
is held up by their unfavorable properties like stability, poor water solubility, low absorption, and
quick metabolism. Nonetheless, the advancement of nanotechnology-based innovative nanocarrier formulations
has improved the phytomedicines’ profile to be used in the treatment of liver cancer. Nanocarriers
not only improve the solubility and stability of phytomedicines but also extend their residence in
plasma and accomplish specificity. In this review, we summarize the advancements introduced by
nanotechnology in the treatment of liver cancer. In particular, we discuss quite a few applications of
nanophytomedicines like curcumin, quercetin, epigallocatechin-3-gallate, berberine, apigenin, triptolide,
and resveratrol in liver cancer treatment.
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Affiliation(s)
- Sachin Kumar
- Department of Pharmacology, Delhi Institute of Pharmaceutical Sciences and Research, Sector-III, MB Road, PushpVihar, New Delhi-110017, India
| | - Faizana Fayaz
- Department of Pharmaceutical Chemistry, Delhi Institute of Pharmaceutical Sciences and Research, Sector-III, MB Road, PushpVihar, New Delhi-110017, India
| | - Faheem Hyder Pottoo
- Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, P.O. Box 1982, Dammam, 31441, Saudi Arabia
| | - Sakshi Bajaj
- Department of Herbal Drug Technology, Delhi Institute of Pharmaceutical Sciences and Research, Sector-III, MB Road, PushpVihar, New Delhi-110017, India
| | - Satish Manchanda
- Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research, Sector-III, MB Road, PushpVihar, New Delhi-110017, India
| | - Himangini Bansal
- Department of Pharmaceutical Chemistry, Delhi Institute of Pharmaceutical Sciences and Research, Sector-III, MB Road, PushpVihar, New Delhi-110017, India
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Wu F, Xue H, Li X, Diao W, Jiang B, Wang W, Yu W, Bai J, Wang Y, Lian B, Feng W, Sun T, Qu M, Zhao C, Wang Y, Wu J, Gao Z. Enhanced targeted delivery of adenine to hepatocellular carcinoma using glycyrrhetinic acid-functionalized nanoparticles in vivo and in vitro. Biomed Pharmacother 2020; 131:110682. [PMID: 32947204 DOI: 10.1016/j.biopha.2020.110682] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Revised: 08/15/2020] [Accepted: 08/20/2020] [Indexed: 12/24/2022] Open
Abstract
Hepatocellular carcinoma (HCC), a common malignancy in China and globally, is primarily treated through surgical resection and liver transplantation, with chemotherapy as a significant synergistic option. Adenine (Ade), a nucleobase, exhibits antitumor effects by blocking human hepatic carcinoma cells in S phase and inhibiting tumor cell proliferation. However, its use is limited owing to its low solubility, poor targeting ability, and nephrotoxicity. Therefore, liver-targeting drug delivery systems have attracted considerable attention for the treatment of HCC. In this study, we explored the liver-targeting efficacy and antitumor effect of adenine-loaded glycyrrhetinic acid-modified hyaluronic acid (Ade/GA-HA) nanoparticles in vitro and in vivo. The GA-HA nanoparticles possessed obvious targeting specificity toward liver cancer cells, which was mainly achieved by the specific binding of the GA ligand to the GA receptor that was highly expressed on the liver cell membrane. In vitro and in vivo results showed that Ade/GA-HA nanoparticles could inhibit liver cancer cell proliferation and migration, promote apoptosis, and significantly inhibit the growth of tumor tissues. Altogether, this study is the first to successfully demonstrate that the targeting activity and antitumor effect of Ade against HCC are enhanced by using GA-HA nanoparticles in vitro and in vivo.
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Affiliation(s)
- Fei Wu
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China
| | - Hantao Xue
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China
| | - Xiaocheng Li
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China
| | - Wenbin Diao
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China
| | - Bin Jiang
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China
| | - Weiyu Wang
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China
| | - Wenjing Yu
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China
| | - Jingkun Bai
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China
| | - Yi Wang
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China
| | - Bo Lian
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China
| | - Weiguo Feng
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China
| | - Tongyi Sun
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China
| | - Meihua Qu
- Translational Medical Center, Weifang Second People's Hospital, Weifang Respiratory Disease Hospital, Weifang 261041, China
| | - Chunling Zhao
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China
| | - Yubing Wang
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China.
| | - Jingliang Wu
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China.
| | - Zhiqin Gao
- School of Bioscience and Technology, Weifang Medical University, Weifang, Shandong Province, China.
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Elzoghby AO, Abdelmoneem MA, Hassanin IA, Abd Elwakil MM, Elnaggar MA, Mokhtar S, Fang JY, Elkhodairy KA. Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier & targeting ligand. Biomaterials 2020; 263:120355. [PMID: 32932142 PMCID: PMC7480805 DOI: 10.1016/j.biomaterials.2020.120355] [Citation(s) in RCA: 109] [Impact Index Per Article: 21.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Revised: 08/18/2020] [Accepted: 08/31/2020] [Indexed: 12/21/2022]
Abstract
Recent progress in protein-based nanomedicine, inspired by the success of Abraxane® albumin-paclitaxel nanoparticles, have resulted in novel therapeutics used for treatment of challenging diseases like cancer and viral infections. However, absence of specific drug targeting, poor pharmacokinetics, premature drug release, and off-target toxicity are still formidable challenges in the clinic. Therefore, alternative protein-based nanomedicines were developed to overcome those challenges. In this regard, lactoferrin (Lf), a glycoprotein of transferrin family, offers a promising biodegradable well tolerated material that could be exploited both as an active therapeutic and drug nanocarrier. This review highlights the major pharmacological actions of Lf including anti-cancer, antiviral, and immunomodulatory actions. Delivery technologies of Lf to improve its pries and enhance its efficacy were also reviewed. Moreover, different nano-engineering strategies used for fabrication of drug-loaded Lf nanocarriers were discussed. In addition, the use of Lf for functionalization of drug nanocarriers with emphasis on tumor-targeted drug delivery was illustrated. Besides its wide application in oncology nano-therapeutics, we discussed the recent advances of Lf-based nanocarriers as efficient platforms for delivery of anti-parkinsonian, anti-Alzheimer, anti-viral drugs, immunomodulatory and bone engineering applications.
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Affiliation(s)
- Ahmed O Elzoghby
- Center for Engineered Therapeutics, Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA; Harvard-MIT Division of Health Sciences & Technology (HST), Cambridge, MA, 02139, USA; Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt.
| | - Mona A Abdelmoneem
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Pharmaceutics, Faculty of Pharmacy, Damanhur University, Damanhur, 22516, Egypt
| | - Islam A Hassanin
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, 21526, Egypt
| | - Mahmoud M Abd Elwakil
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Laboratory of Innovative Nanomedicine, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo, 060-0812, Japan
| | - Manar A Elnaggar
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Nanotechnology Program, School of Sciences & Engineering, The American University in Cairo (AUC), New Cairo, 11835, Egypt
| | - Sarah Mokhtar
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
| | - Jia-You Fang
- Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Taoyuan, 333, Taiwan; Research Center for Industry of Human Ecology, Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, 333, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, 333, Taiwan
| | - Kadria A Elkhodairy
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
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Lactoferrin-dual drug nanoconjugate: Synergistic anti-tumor efficacy of docetaxel and the NF-κB inhibitor celastrol. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 118:111422. [PMID: 33255023 DOI: 10.1016/j.msec.2020.111422] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 07/27/2020] [Accepted: 08/19/2020] [Indexed: 12/12/2022]
Abstract
Despite the progress in cancer nanotherapeutics, some obstacles still impede the success of nanocarriers and hinder their clinical translation. Low drug loading, premature drug release, off-target toxicity and multi-drug resistance are among the most difficult challenges. Lactoferrin (LF) has demonstrated a great tumor targeting capacity via its high binding affinity to low density lipoprotein (LDL) and transferrin (Tf) receptors overexpressed by various cancer cells. Herein, docetaxel (DTX) and celastrol (CST) could be successfully conjugated to LF backbone for synergistic breast cancer therapy. Most importantly, the conjugate self-assembled forming nanoparticles of 157.8 nm with elevated loading for both drugs (6.94 and 5.98% for DTX and CST, respectively) without risk of nanocarrier instability. Moreover, the nanoconjugate demonstrated enhanced in vivo anti-tumor efficacy in breast cancer-bearing mice, as reflected by a reduction in tumor volume, prolonged survival rate and significant suppression of NF-κB p65, TNF-α, COX-2 and Ki-67 expression levels compared to the group given free combined DTX/CST therapy and to positive control. This study demonstrated the proof-of-principle for dual drug coupling to LF as a versatile nanoplatform that could augment their synergistic anticancer efficacy.
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Kondapi AK. Targeting cancer with lactoferrin nanoparticles: recent advances. Nanomedicine (Lond) 2020; 15:2071-2083. [PMID: 32779524 DOI: 10.2217/nnm-2020-0090] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Lactoferrin, an iron storage protein, is known for its microbicidal activity and its ability to modulate the immune system, mediated through specific interactions with receptors on cell surfaces for internalization. These activities confer a significant versatility to lactoferrin, presenting it as a targeting ligand to disease-bearing cells. Early efforts in developing targeted delivery systems have focused on nano- and microcomposites comprised of metal and polymeric materials. These can be targeted through conjugation or adsorption of lactoferrin to achieve recognition to receptor-expressing cells. More recently, efforts are underway to utilize lactoferrin itself as a medium in loading the therapeutic agent. The functional efficiency of drug-loaded lactoferrin nanoparticles has been evaluated in different disease conditions such as cancer, HIV, Parkinson's disease, etc. This review will present the details of composition and performance of various delivery systems designed and developed using lactoferrin as targeting agent for the treatment of cancer.
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Affiliation(s)
- Anand K Kondapi
- Department of Biotechnology & Bioinformatics, School of Life Sciences, University of Hyderabad, Hyderabad, 500046, India.,Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA
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Gaber M, Elhasany KA, Sabra S, Helmy MW, Fang JY, Khattab SN, Bekhit AA, Teleb M, Elkodairy KA, Elzoghby AO. Co-Administration of Tretinoin Enhances the Anti-Cancer Efficacy of Etoposide via Tumor-Targeted Green Nano-Micelles. Colloids Surf B Biointerfaces 2020; 192:110997. [PMID: 32361378 DOI: 10.1016/j.colsurfb.2020.110997] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2019] [Revised: 02/20/2020] [Accepted: 03/24/2020] [Indexed: 12/29/2022]
Abstract
Herein we report promoted anti-cancer activity via a combination strategy of synergistic chemotherapy/retinoid-based breast cancer therapy with shell-stabilized micellar green nanomedicine. Amphiphilic zein-chondroitin sulfate (ChS)-based copolymeric micelles (PMs) were successfully developed via carbodiimide coupling for concomitant delivery of etoposide (ETP) and all-trans retinoic acid (ATRA) to breast cancer. The micelles exhibited low critical micellar concentration (CMC) of 0.008 mg/mL with high encapsulation efficiencies of ETP and ATRA (61.2 and 84.29%, respectively). Calcium-mediated crosslinking of the anionic ChS micellar shell resulted in prolonged drug release with small micellar size of 222.7 nm. The micelles exhibited augmented internalization into MCF-7 breast cancer cells by virtue of ChS binding affinity to CD44 receptors overexpressed by cancer cells. Consequently, the ETP/ATRA-loaded micelles exhibited synergistic cytotoxicity against breast cancer cells as revealed by their significantly lower IC50, combination index (CI), and higherdose reduction index (DRI) in comparison to the free ETP and free ATRA or their combination. Micelles displayed superiority in reducing tumor volume, decreasing proliferation, and promoting necrosis in mice bearing Ehrlich Ascites Tumor (EAT) upon comparison to free ETP and free ATRA or their combination. Overall, the developed green zein-ChS micelles offer a promising platform for tumor-targeted delivery of hydrophobic therapeutic agents.
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Affiliation(s)
- Mohamed Gaber
- Department of Cancer Biology, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA; Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
| | - Kholod A Elhasany
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
| | - Saly Sabra
- Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, 21526, Egypt
| | - Maged W Helmy
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Pharmacology and Toxicology, Faculty of Pharmacy, Damanhur University, Damanhur, Egypt
| | - Jia-You Fang
- Pharmaceutics Laboratory, Graduate Institute of Natural Products, Chang Gung University, Taoyuan, 333, Taiwan; Research Center for Industry of Human Ecology, Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, 333, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Kweishan, Taoyuan, 333, Taiwan
| | - Sherine N Khattab
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Chemistry, Faculty of Science, Alexandria University, Alexandria, 21321, Egypt.
| | - Adnan A Bekhit
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
| | - Mohamed Teleb
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Biotechnology, Institute of Graduate Studies and Research, Alexandria University, Alexandria, 21526, Egypt
| | - Kadria A Elkodairy
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt
| | - Ahmed O Elzoghby
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, 21521, Egypt; Division of Engineering in Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Harvard-MIT Division of Health Sciences & Technology (HST), Cambridge, MA 02139, USA.
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Yu XN, Deng Y, Zhang GC, Liu J, Liu TT, Dong L, Zhu CF, Shen XZ, Li YH, Zhu JM. Sorafenib-Conjugated Zinc Phthalocyanine Based Nanocapsule for Trimodal Therapy in an Orthotopic Hepatocellular Carcinoma Xenograft Mouse Model. ACS APPLIED MATERIALS & INTERFACES 2020; 12:17193-17206. [PMID: 32207914 DOI: 10.1021/acsami.0c00375] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Sorafenib, a multitargeted kinase inhibitor, has been reported to elicit a limited therapeutic effect in hepatocellular carcinoma (HCC). Currently, phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is emerging as a powerful modality for cancer therapy. However, few studies have been reported the effectiveness of the combination of sorafenib with PDT and PTT in HCC. Herein, we designed and synthesized bovine serum albumin (BSA)-coated zinc phthalocyanine (ZnPc) and sorafenib (SFB) nanoparticle (ZnPc/SFB@BSA). The obtained ZnPc/SFB@BSA was able to trigger PDT, PTT, and chemotherapy. After irradiation by a 730 nm light, ZnPc/SFB@BSA significantly suppressed HCC cell proliferation and metastasis while promoted cell apoptosis in vitro. Furthermore, intravenous injection of ZnPc/SFB@BSA led to dramatically reduced tumor growth in an orthotopic xenograft HCC model. More importantly, ZnPc/SFB@BSA presented low toxicity and adequate blood compatibility. Therefore, a combination of ZnPc with sorafenib via BSA-assembled nanoparticle can markedly suppress HCC growth, representing a promising strategy for HCC patients.
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Affiliation(s)
- Xiang-Nan Yu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
- Shanghai Institute of Liver Disease, Shanghai 200032, China
| | - Yong Deng
- Institute of Bismuth Science & College of Science, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Guang-Cong Zhang
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
- Shanghai Institute of Liver Disease, Shanghai 200032, China
| | - Jie Liu
- Institute of Bismuth Science & College of Science, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Tao-Tao Liu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
- Shanghai Institute of Liver Disease, Shanghai 200032, China
| | - Ling Dong
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
- Shanghai Institute of Liver Disease, Shanghai 200032, China
| | - Chang-Feng Zhu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
- Shanghai Institute of Liver Disease, Shanghai 200032, China
| | - Xi-Zhong Shen
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
- Shanghai Institute of Liver Disease, Shanghai 200032, China
- Key Laboratory of Medical Molecular Virology, Shanghai Medical College of Fudan University, Shanghai 200032, China
| | - Yu-Hao Li
- Institute of Bismuth Science & College of Science, University of Shanghai for Science and Technology, Shanghai 200093, China
| | - Ji-Min Zhu
- Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai 200032, China
- Shanghai Institute of Liver Disease, Shanghai 200032, China
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Haggag YA, Ibrahim RR, Hafiz AA. Design, Formulation and in vivo Evaluation of Novel Honokiol-Loaded PEGylated PLGA Nanocapsules for Treatment of Breast Cancer. Int J Nanomedicine 2020; 15:1625-1642. [PMID: 32210557 PMCID: PMC7069567 DOI: 10.2147/ijn.s241428] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2019] [Accepted: 02/13/2020] [Indexed: 01/11/2023] Open
Abstract
Background Honokiol (HK) is a common herbal medicine extracted from magnolia plants. Low aqueous solubility and limited bioavailability of HK have hindered its clinical application, especially for cancer treatment. Nano-drug delivery system has the potential to enhance HK delivery and therefore, enhance its anti-cancer activity. Purpose The study’s aim is to design novel PEGylated-PLGA polymeric nanocapsules (NCs) for HK delivery to breast tumor-bearing mice after systemic administration. Methods Formulation of different HK-loaded NCs and their physio-chemical characterization were optimized through the use of different formulation variables. The antitumor activity of the HK-loaded NCs was investigated both in vitro using MCF-7 and EAC breast cancer cell lines and in vivo using solid Ehrlich carcinoma (SEC) breast cancer model. Results The optimum HK-loaded NCs were prepared from 15% PEG-PLGA diblock copolymer and exhibited the lowest nano size of 125 nm, smooth spherical morphology, highest drug loading of 94% and highest cellular uptake into breast cancer cells. HK-loaded PEGylated NCs can effectively inhibit the in vitro cell growth of breast cancer cells by 80.2% and 58.1% compared to 35% and 31% with free HK in the case of MCF-7 and EAC, respectively. HK-loaded NCs inhibited SEC tumor growth by 2.3 fold significantly higher than free HK, in vivo. Conclusion The designed drug delivery system encapsulating HK exhibited a pronounced decrease in tumor growth biomarkers meanwhile proved its safety in animals. Therefore, 15% PEGylated HK-loaded NCs may act as a promising new approach for breast cancer treatment.
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Affiliation(s)
- Yusuf A Haggag
- Department of Pharmaceutical Technology, Faculty of Pharmacy, Tanta University, Tanta, Egypt
| | - Rowida R Ibrahim
- Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Tanta University, Tanta, Egypt
| | - Amin A Hafiz
- Department of Clinical Nutrition, Faculty of Applied Medical Sciences, Umm Al-Qura University, Mecca, Kingdom of Saudi Arabia
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Stem Cell Therapy for Hepatocellular Carcinoma: Future Perspectives. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1237:97-119. [PMID: 31728916 DOI: 10.1007/5584_2019_441] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common types of cancer and results in a high mortality rate worldwide. Unfortunately, most cases of HCC are diagnosed in an advanced stage, resulting in a poor prognosis and ineffective treatment. HCC is often resistant to both radiotherapy and chemotherapy, resulting in a high recurrence rate. Although the use of stem cells is evolving into a potentially effective approach for the treatment of cancer, few studies on stem cell therapy in HCC have been published. The administration of stem cells from bone marrow, adipose tissue, the amnion, and the umbilical cord to experimental animal models of HCC has not yielded consistent responses. However, it is possible to induce the apoptosis of cancer cells, repress angiogenesis, and cause tumor regression by administration of genetically modified stem cells. New alternative approaches to cancer therapy, such as the use of stem cell derivatives, exosomes or stem cell extracts, have been proposed. In this review, we highlight these experimental approaches for the use of stem cells as a vehicle for local drug delivery.
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Hafez DA, Elkhodairy KA, Teleb M, Elzoghby AO. Nanomedicine-based approaches for improved delivery of phyto-therapeutics for cancer therapy. Expert Opin Drug Deliv 2020; 17:279-285. [DOI: 10.1080/17425247.2020.1723542] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Dina A. Hafez
- Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Kadria A. Elkhodairy
- Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Mohamed Teleb
- Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
| | - Ahmed O. Elzoghby
- Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
- Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria, Egypt
- Division of Engineering in Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA
- Harvard-MIT Division of Health Sciences & Technology (HST), Cambridge, MA, USA
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