Rheumatoid arthritis (RA) is an inflammatory immune-triggered disease that causes synovitis, cartilage degradation, and joint injury. In nanotechnology, conventional liposomes were extensively investigated for RA. However, they frequently undergo rapid clearance, reducing circulation time and therapeutic efficacy. Additionally, their stability in the bloodstream is often compromised, resulting in premature drug release. The current review explores the potential of targeted liposomal-based nanosystems in the treatment of RA. It highlights the pathophysiology of RA, explores selective targeting sites, and elucidates diverse mechanisms of novel liposomal types and their applications. Furthermore, the targeting strategies of pH-sensitive, flexible, surface-modified, PEGylated, acoustic, ROS-mediated, and biofunctionalized liposomes are addressed. Targeted nanoliposomes showed potential in precisely delivering drugs to CD44, SR-A, FR-β, FLS, and toll-like receptors through the high affinity of ligands. In vitro studies interpreted stable release profiles and improved stability. Ex vivo studies on skin demonstrated that ultradeformable and glycerol-conjugated liposomes enhanced drug penetrability. In vivo experiments for liposomal types in the arthritis rat model depicted remarkable efficacy in reducing joint swelling, pro-inflammatory cytokines, and synovial hyperplasia. In conclusion, these targeted liposomes represented a significant leap forward in drug delivery, offering effective therapeutic options for RA. In the future, integrating these advanced liposomes with artificial intelligence, immunotherapy, and precision medicine holds great promise.

This study introduces a novel approach to enhance the antibacterial properties of UIO-66 by incorporating both Thymol and ZnO nanoparticles within its framework which represents a significant advancement like exhibiting a synergistic antibacterial effect, providing a prolonged and controlled release, and mitigating cytotoxicity associated with the release of free ZnO nanoparticles by combining these two antimicrobial agents within a single, well-defined metal-organic framework. UIO-66 frameworks are investigated as carriers for the natural antimicrobial agent, Thymol, and ZnONPs offering a novel drug delivery system for antibacterial applications. Results demonstrated 132, 90, 184, and 223 nm sizes for UIO-66, ZnONPs, UIO-66 encapsulated Thymol, and UIO-66 encapsulated both Thymol and ZnONPs, respectively. Successful encapsulation of the antibacterial drug with a high entrapment efficiency of 64 % for Thymol was approved, and 49 % in-vitro release of Thymol was achieved for 72 hours. In-vitro antibacterial assays revealed promising results, with the drug-loaded nanoparticles exhibiting significantly lower MIC values and enhanced bactericidal activity against S. Aureus bacterial strains compared to the free drug, as demonstrated by agar disk diffusion and time-kill assays. MIC values reduced from a range of 31.25-250 µg/ml for free Thymol and 12.5-100 µg/ml for free ZnONPs to 3.9-62.5 µg/ml for Thymol@UIO-66 and 1.95-15.63 µg/ml for Thymol/ZnONPs@UIO-66. According to the results, the mixture of both Thymol and ZnONPs had 41 % and 16 % more antibiofilm activities in comparison with free Thymol and free ZnONPs, respectively. Furthermore, Thymol@UIO-66 had 25 % higher antibiofilm activities relative to not-encapsulated Thymol and ZnONPs, and this improvement was even 46 % more in Thymol/ZnONPs@UIO-66 in comparison with Thymol@UIO-66. Overall, this study demonstrates the potential of Thymol/ZnONPs@UIO-66 frameworks as a promising drug delivery platform for effective antibacterial therapy. This approach to overcome antibiotic resistance and improve treatment efficacy potentially.

Osteoimmunomodulation is a strategy to promote bone regeneration in implants by modifying the immune environment. CpG-containing oligonucleotides type C (CpG ODN C) and Polyinosinic:polycytidylic acid (Poly[I:C]) are analogs of microbial nucleic acids that have been studied for various immunotherapeutic applications. This research investigates the potential of CpG ODN C and Poly(I:C) as an osteoimmunomodulatory agent for bone regenerative purposes. We encapsulated each nucleic acid in a lipid-based nanoparticle to facilitate the delivery into intracellular pathogen recognition receptors in immune cells. The lipid-based nanoparticles were ±250 nm in size with a negative charge (-36 to -40 mV) and an encapsulation efficiency of ±60 %. Lipid-based nanoparticles containing nucleic acids, Lip/CpG ODN C and Lip/Poly(I:C), increased the production of TNF, IL-6, and IL-10 by primary human macrophages compared to free-form nucleic acids. Conditioned medium from macrophages treated with CpG ODN C (10 µg/ml) and Lip/CpG ODN C (0.1, 1, and 10 µg/ml) promoted osteoblast differentiation of human mesenchymal stromal cells by 2.6-fold and 3-fold, respectively; no effect was seen for Lip/Poly(I:C). Bone implants were prepared, consisting of a biphasic calcium phosphate scaffold, bone morphogenetic protein (BMP) 2, and lipid-based nanoparticles suspended in gelatin methacryloyl (GelMA) hydrogel. Implants were evaluated for de novo bone formation in an extra-skeletal implantation model in rabbits for 5 weeks. Based on the particles suspended in GelMA, six groups of implants were prepared: Lip/CpG ODN C, Lip/Poly(I:C), Lip (empty), CpG ODN C, Poly(I:C), and a control group consisting of empty GelMA. After 5 weeks, healthy bone tissue formed in all of the implants with active osteoblast and osteoclast activity, however, the amount of new bone volume and scaffold degradation were similar for all implants. We suggest that the working concentrations of the nucleic acids employed were inadequate to induce a relevant inflammatory response. Additionally, the dosage of BMP-2 used may potentially mask the immune-stimulatory effect. Lip/CpG ODN C holds potential as a bioactive agent for osteoimmunomodulation, although further in vivo demonstration should corroborate the current in vitro findings.

Many clinical tumors exhibit a vascular endothelium covered by mural cells and stroma with abundant collagen fibers, which greatly inhibit the penetration of nanoparticle drug delivery systems (DDS) formulations deep into the tumors. We previously found that Salmonella typhimurium VNP20009 attracting attention as live bacterial therapeutics, which is a novel pharmaceutical modality for cancer treatment, can grow within deep tumors with abundant stroma and tight vasculature. Because this finding interestingly indicates that VNP20009 administration disrupts vascular and stromal structures even in refractory tumors, we investigated the possibility that VNP20009 administration improves DDS formulations migrations into tumors in this study. VNP20009 co-administration drastically improved the translocation and diffusion of liposomes deep into the tumors, particularly in stroma-rich xenografted tumors, indicating its tumor stromal opening ability. Furthermore, this approach can completely inhibit tumors in various refractory tumor models, including pancreatic cancers, using liposomal doxorubicin (Doxil®) and liposomal irinotecan (Onivyde®). Notably, this remarkable anticancer effect is not simply attributed to the therapeutic effects of liposomal anticancer drugs and VNP20009, but it involves an additional effect, improving the intratumor pharmacokinetics of liposomal anticancer drugs following VNP20009 co-administration. The unique tumor stromal opening ability of VNP20009 demonstrated in this study is a promising strategy for resolving the major challenges faced by tumor DDS.

The application of metal-organic frameworks (MOFs) as drug delivery systems with a high drug-loading capacity and targeted delivery is advancing rapidly. This study is the first to elucidate the mechanism of drug-loading in MOFs. It focused on the crucial role of solvents in drug-loading capacity. Ibuprofen, which is widely used as a nonsteroidal antiflammatory drug, was selected as a model drug. The drug-loading capacities of zeolitic imidazolate framework-8 (ZIF-8) and Universitetet i Oslo-66-NH2 (UiO-66-NH2) were investigated in various solvents. For ZIF-8, an increase in the solvent dipole moment corresponded to an increase in the drug-loading capacity. Intriguingly, the converse trend was observed for UiO-66-NH2. Therein, a decrease in the solvent dipole moment caused an increase in the drug-loading. These observations indicated that the solvent dipole moment plays a critical role in the drug-loading mechanism of the MOFs. Furthermore, Raman spectroscopy in the solvents with different polarities revealed significant variations in the molecular vibrations of ZIF-8 and UiO-66-NH2. It was indicated that in both the MOFs, the drug-loading amount increased in the solvents when the molecular vibrations of the MOF were constrained. This study revealed that the solvent plays a crucial role in the drug-loading in MOFs, and the polarity of the solvents contributes significantly to the molecular vibration of MOFs during drug-loading, thereby affecting the drug-loading capacity.

Current research in nanotechnology is improving or developing novel applications that could improve disease diagnosis or treatment. This study highlights several nanoscale drug delivery technologies, such as nano micelles, nanocapsules, nanoparticles, liposomes, branching dendrimers, and nanostructured lipid formulations for the targeted therapy of ovarian cancer (OC), to overcome the limitations of traditional delivery. Because traditional drug delivery to malignant cells has intrinsic flaws, new nanotechnological-based treatments have been developed to address these conditions. Ovarian cancer is the most common gynecological cancer and has a higher death rate because of its late diagnosis and recurrence. This review emphasizes the discipline of medical nanotechnology, which has made great strides in recent years to solve current issues and enhance the detection and treatment of many diseases, including cancer. This system has the potential to provide real-time monitoring and diagnostics for ovarian cancer treatment, as well as simultaneous delivery of therapeutic agents.

Lipid-based nanoparticles have emerged as promising drug delivery systems for a wide range of therapeutic agents, including plasmids, mRNA, and proteins. However, these nanoparticles still encounter various challenges in drug delivery, including drug leakage, poor solubility, and inadequate target specificity. In this comprehensive review, we present an in-depth investigation of four distinct drug delivery methods: liposomes, lipid nanoparticle formulations, solid lipid nanoparticles, and nanoemulsions. Moreover, we explore recent advances in lipid-based nanomedicines (LBNs) for organ-specific delivery, employing ligand-functionalized particles that specifically target receptors in desired organs. Through this strategy, LBNs enable direct and efficient drug delivery to the intended organs, leading to superior DNA or mRNA expression outcomes compared to conventional approaches. Importantly, the development of novel ligands and their judicious combination holds promise for minimizing the side effects associated with nonspecific drug delivery. By leveraging the unique properties of lipid-based nanoparticles and optimizing their design, researchers can overcome the limitations associated with current drug delivery systems. In this review, we aim to provide valuable insights into the advancements, challenges, and future directions of lipid-based nanoparticles in the field of drug delivery, paving the way for enhanced therapeutic strategies with improved efficacy and reduced adverse effects.

Biological barriers significantly impede the delivery of nanotherapeutics to diseased tissues, diminishing therapeutic efficacy across pathologies such as cancer and inflammatory disorders. Although conventional strategies integrate multifunctional designs and molecular components into nanomaterials (NMs), many approaches remain insufficient to overcome these barriers. Key challenges, including inadequate drug accumulation at target sites and nonspecific biodistribution, persist in nanotherapeutic development. NMs, which harness the ability to precisely modulate drug delivery spatiotemporally and control release kinetics, represent a transformative platform for targeted cancer therapy. In this review, we highlight the biological obstacles limiting effective cancer treatment and evaluate how stimuli-responsive NMs address these constraints. By leveraging exogenous and endogenous stimuli, such NMs improve therapeutic specificity, reduce off-target effects, and amplify drug activity within pathological microenvironments. We systematically analyze the rational design and synthesis of stimuli-responsive NMs, driven by advances in oncology, biomaterials science, and nanoscale engineering. Furthermore, we highlight advances across NM classes-including polymeric, lipid-based, inorganic, and hybrid systems and explore functionalization approaches using targeting ligands, antibodies, and biomimetic coatings. Diverse delivery strategies are evaluated, such as small-molecule prodrug activation, peptide- and protein-based targeting, nucleic acid payloads, and engineered cell-mediated transport. Despite the promise of stimuli-responsive NMs, challenges such as biocompatibility, scalable fabrication, and clinical translation barriers must be addressed. By elucidating structure-function relationships and refining stimulus-triggered mechanisms, these NMs pave the way for transformative precision oncology strategies, enabling patient-specific therapies with enhanced efficacy and safety. This synthesis of interdisciplinary insights aims to catalyze innovation in next-generation nanomedicine for cancer treatment.

Acute myeloid leukemia (AML) is a hematologic malignancy characterized by uncontrolled proliferation of abnormal myeloid cells with a generally poor prognosis despite advancements in chemotherapy and stem cell transplantation. To enhance therapeutic efficacy and minimize systemic toxicity, we designed liposomal nanoparticles functionalized with two distinct targeting ligands, a DNA aptamer or fragment-antigen-binding (Fab) antibody, targeting the surface marker transmembrane glycoprotein CD33 antigen (CD33) on AML cells. Aptamer- and Fab-conjugated liposomes (Apt-Lipm and Fab-Lipm, respectively) were prepared and tested for cellular uptake by CD33-positive AML cell lines. Comparative studies revealed that Fab-Lipm exhibited significantly superior binding affinity, targeting efficiency, and cellular uptake compared with Apt-Lipm. Furthermore, we demonstrated the intracellular distribution and endocytic pathways of Fab-Lipm during the cellular uptake. This comparative study of aptamer- and Fab-conjugated liposomes suggests that the Fab-conjugated liposomal system offers enhanced precision in targeting AML cells for the development of effective therapeutic strategies against hematologic malignancies.

Prostate cancer is the most common malignancy in men worldwide and docetaxel (DTX) is the treatment of choice. However, both the drug and formulation excipients for drug solubilization can cause side effects. In this context, the development of polymeric nanoparticles offers advantages to improve drug delivery and reduce toxicity. In the present work, factorial design was used to evaluate the effect of the amount of poly(L-lactide-co-glycolide) (PLGA) or poly(L-lactide-co-glycolide acid-polyethylene glycol) (PLGA-PEG), D-Alpha-Tocopheryl Polyethylene Glycol Succinate (TPGS) and ratio between aqueous and oily phases on the nanoparticle characteristics. The nanocarriers were characterized regarding particle size, polydispersity, zeta potential, DTX encapsulation efficiency, morphology by transmission electron microscopy, DSC, TGA and FTIR. It was evaluated in vitro for cytotoxicity and cellular uptake in prostate cancer cells. Pegylated nanoparticles, which have a different composition (TPGS%, AP:OP ratio), reduced the nanoparticle size to 105.97 ± 5.16 nm, in PDI 0.13 ± 0.03, zeta potential of -34.73 ± 1.19 mV and increased the encapsulation efficiency to 96.78 ± 1.20%. Characterization by DSC, TGA and FTIR confirmed drug encapsulation and showed colloidal stability. Pegylated nanoparticles were more stable upon serum incubation and adsorbed less proteins. In conclusion, the pegylation of the nanoparticles affected the physicochemical parameters. Also, the pegylation of nanoparticles decreased uptake by macrophages. Finally, cellular uptake and cell cytotoxicity were higher in tumor cells when compared to non-tumor cells, although they were not affected by pegylation.

Nanomotors driven by endogenous enzymes are favored in biology and pharmacy due to their spontaneous driving and efficient biocatalytic activity, and have potential applications in the treatment of clinical diseases that are highly dependent on targeted effects. For diseases such as muscle atrophy, using energy molecules such as ATP to improve cellular metabolism is a relatively efficient treatment method. However, traditional adenosine triphosphate (ATP) therapies for muscle atrophy face limitations due to instability under physiological conditions and poor targeting efficiency. To address these challenges, we developed an endogenous proton-gradient-driven ATP transport motor (ATM), a nanomotor integrating chloroplast-derived FoF1-ATPase with a biocompatible flask-shaped organic shell (FOS). The ATM is synthesized by vacuum-injecting phospholipid-embedded FoF1-ATPase nanothylakoids into ribose-based FOS, enabling autonomous propulsion in acidic microenvironments through proton-driven negative chemotaxis (directional movement away from regions of higher proton concentration). This nanomotor converts proton gradients into ATP synthesis, directly replenishing cellular energy deficits in atrophic tissues. In vitro studies demonstrated high biocompatibility (>90% cell viability at 150 μg/mL) and pH-responsive motility, achieving speeds up to 4.32 μm/s under physiological gradients (ΔpH = 3). In vivo experiments using dexamethasone-induced muscle atrophy mice revealed that ATM treatment accelerated weight recovery and restored normal muscle morphology, with treated mice exhibiting cell sizes comparable to healthy controls (30-40 μm vs. 15-25 μm in untreated). These results highlight the ATM's potential as a precision therapeutic platform for metabolic disorders, leveraging the natural enzyme functionality and synthetic material design to enhance efficacy while minimizing systemic toxicity.

Hyperlipidemia, a critical risk factor for various health conditions, necessitates innovative therapeutic strategies. Investigating the effectiveness of liposomal formulations in managing hyperlipidemia is essential. Resveratrol (RES)-loaded nanoliposomes present a promising new approach for hyperlipidemia treatment. In this study, we investigated the anti-hyperlipidemic potential of RES-loaded nanoliposomes in high-fat diet (HFD)-fed rats. The nanoliposomes were prepared using a thin-film hydration method. According to transmission electron microscopy (TEM) and dynamic light scattering (DLS) results, the mean size of prepared RES-loaded nanoliposomes were about 42 nm and 68 nm, respectively, with a zeta potential of -65.6 mV. The entrapment efficiency and loading content were 83.78% and 14.25%, respectively. Additionally, the RES-loaded nanoliposomes exhibited controlled release kinetics compared to the free RES form. Moreover, in a hyperlipidemic rat model induced by an HFD, orally administered RES-loaded nanoliposomes significantly reduced total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), and triglycerides (TG), while concurrently increasing high-density lipoprotein cholesterol (HDL-C) levels. Additionally, liver damage induced by HFD was alleviated by RES-loaded nanoliposomes. The expression levels of Toll-like receptor 3 (TLR3) and TIR domain-containing adaptor-inducing interferon-β (TRIF) were assessed using fluorescence immunohistochemistry. Notably, RES-loaded nanoliposomes significantly reduced the expression of these protein. The effect of RES-loaded nanoliposomes was measured on body weight of HFD rats, demonstrting RES-loaded nanoliposomes hold promise for weight management. These findings underscore the potential of RES-loaded nanoliposomes as a safe and effective therapeutic option for hyperlipidemia.

Metal-Organic Frameworks (MOFs), as a new type of porous material, have attracted widespread attention in the fields of chemistry, materials science, and biomedicine owing to their unique structural characteristics and potential for functionalization. This review summarizes the latest research progress of MOFs in the field of steroid compounds, including the latest research progress of MOFs in the purification and separation of steroids, sensing and detection, catalytic transformation, and drug delivery. First, we explore how the porous structure and chemical functionalization of MOFs achieve efficient separation and purification of steroid compounds. Second, the high sensitivity and selectivity of MOFs as sensing materials in steroid detection, as well as their application potential in actual sample analysis, are analyzed. Furthermore, the role of MOFs in steroid catalytic transformation reactions is discussed, including their performance as catalysts or catalyst carriers. Finally, we focus on the innovative applications of MOFs in drug delivery systems, especially their advantages in controlled release and targeted drug delivery. This article also explores the future development trends and application prospects of MOFs in the field of steroids, highlighting the challenges and opportunities in material design, functionalization strategies, and practical implementations. Through this review, we aim to provide a comprehensive theoretical basis and practical guidance for further research and application of MOFs in the field of steroids.

Preclinical studies on liposomal interleukin (IL) therapy demonstrate considerable promise in cancer treatment. This review explores the achievements, challenges, and future potential of liposomal IL encapsulation, focusing on preclinical studies.

A structured search was conducted using the PubMed and Web of Science databases with the following search terms and Boolean operators: ("liposomal interleukin" OR "liposome-encapsulated interleukin") AND ("gene therapy" OR "gene delivery") AND ("cancer" OR "tumor" OR "oncology") AND ("pre-clinical studies" OR "animal models" OR "in vitro studies".

Liposomal IL-2 formulations are notable for enhancing delivery and retention at tumor sites. Recombinant human interleukin (rhIL-2) adsorbed onto small liposomes (35-50 nm) substantially reduces metastases in murine models. Hepatic metastasis models demonstrate superior efficacy of liposomal IL-2 over free IL-2 by enhancing immune responses, particularly in the liver. Localized delivery strategies, including nebulized liposomal IL-2 in canine pulmonary metastases and intrathoracic administration in murine sarcoma models, reduce systemic toxicity while promoting immune activation and tumor regression. Liposomal IL gene therapy, delivering cytokine genes directly to tumor sites, represents a notable advancement. Combining IL-2 gene therapy with other cytokines, including IL-6 or double-stranded RNA adjuvants, synergistically enhances macrophage and T-cell activation. Liposomal IL-4, IL-6, and IL-21 therapies show potential across various tumor types. Pairing liposomal IL-2 with chemotherapy or immune agents improves remission and survival. Innovative strategies, including PEGylation and ligand-targeted systems, optimize delivery, release, and therapeutic outcomes.

Utilizing immune-stimulatory ILs through advanced liposomal delivery and gene therapy establishes a strong foundation for advancing cancer immunotherapy.

Phospholipids are widely used in food and pharmacological formulations. However, these typically suffer from limitations such as low colloidal stability. Promising stability has been observed for vesicles based on phosphatidylglucose (P-Glu), but fundamental knowledge on this lipid is missing and those observations were made using P-Glu containing mixed acyl groups. The acyl groups are expected to influence the properties of phosphatidylglucose to a large extent.

Using an enzyme-based method, P-Glu containing either palmitic (DPP-Glu), stearic (DSP-Glu) or oleic (DOP-Glu) acid were synthesized. The morphology of the lipid dispersions was studied using small angle x-ray scattering and cryogenic transmission electron microscopy and the data was modelled to extract bilayer structural parameters. Phosphatidylcholine lipids containing the same fatty acids were studied for comparison.

All phosphatidylcholine lipids formed mainly multilamellar vesicles. DOP-Glu formed unilamellar vesicles (ULVs), while disc like objects were observed in the case of DPP-Glu and DSP-Glu formed predominantly bilayer stacks. In the 1:1 mixture of the DOPC and DOP-Glu, ULVs were formed. The bilayer thickness increased as follows: DOP-Glu < DPP-Glu < DSP-Glu and in the PC series the same trend was seen for the lamellar spacing. DSP-Glu had similar lamellar spacing as DSPC.

In this article, we revisit an article, which specifically focuses on the utilization of exosomes derived from human bone marrow mesenchymal stem cells (MSCs) for targeted delivery of gemcitabine in pancreatic cancer treatment. The experimental results demonstrated that the exosome-based drug delivery system derived from MSCs significantly augmented apoptosis in pancreatic cancer cells. The biocompatibility, targeting specificity, and low immunogenicity of exosomes render them as optimal carriers for drug delivery, enabling precise administration of therapeutics to diseased tissues while mitigating adverse effects, thereby achieving targeted treatment of cancer cells and significantly enhancing anti-tumor efficacy. However, the clinical application of exosome drug delivery platforms in oncology still presents challenges, necessitating further optimization to ensure their stability and efficacy. This study focuses on elucidating the advantages of exosomes as a drug delivery platform, exploring the utilization of MSC-derived exosomes in oncology therapy, and discussing their potential and future directions in cancer treatment.

The convergence of artificial intelligence (AI) and nanomedicine has revolutionized the design of smart multifunctional nanocarriers (SMNs) for drug and gene delivery, offering unprecedented precision, efficiency, and personalization in therapeutic applications. AI-driven approaches enhance the development of these nanocarriers by accelerating their design, optimizing drug loading and release kinetics, improving biocompatibility, and predicting interactions with biological barriers. This review explores the transformative role of AI in the fabrication and functionalization of SMNs, emphasizing its impact on overcoming challenges in targeted drug delivery, controlled release, and theranostics. We discuss the integration of AI with advanced nanomaterials-such as polymeric, lipidic, and inorganic nanoparticles-highlighting their potential in oncology and hematology. Furthermore, we examine recent clinical and preclinical case studies demonstrating AI-assisted nanocarrier development for personalized medicine. The synergy between AI and nanotechnology paves the way for next-generation precision therapeutics, addressing critical limitations in traditional drug delivery systems. However, data standardization, regulatory compliance, and translational scalability challenges remain. This review underscores the need for interdisciplinary collaboration to unlock AI's potential in nanomedicine fully, ultimately advancing the clinical application of SMNs for more effective and safer patient care.

The urgent need for safer and innovative antitubercular agents remains a priority for the scientific community. In pursuit of this goal, we designed and evaluated novel 5-phenylfuran-2-carboxylic acid derivatives targeting Mycobacterium tuberculosis (Mtb) salicylate synthase (MbtI), a key enzyme, absent in humans, that plays a crucial role in Mtb virulence. Several potent MbtI inhibitors demonstrating significant antitubercular activity and a favorable safety profile were identified. Structure-guided optimization yielded 5-(3-cyano-5-isobutoxyphenyl)furan-2-carboxylic acid (1e), which exhibited strong MbtI inhibition (IC50 = 11.2 μM) and a promising in vitro antitubercular activity (MIC99 = 32 μM against M. bovis BCG). Esters of 1e were effectively loaded into poly(2-methacryloyloxyethyl phosphorylcholine)-poly(2-(diisopropylamino)ethyl methacrylate) (PMPC-PDPA) polymersomes (POs) and delivered to intracellular mycobacteria, resulting in reduced Mtb viability. This study provides a foundation for the use of POs in the development of future MbtI-targeted therapies for tuberculosis.

Polymersomes have the potential to become the next generation of vesicular drug delivery systems. Their high chemical versatility and in certain cases higher membrane stability than liposomes raised the high hopes for polymersomes as a drug carrier, but the clinical translation has been slow. To jump-start translation, there is a need for meticulous characterization and reporting of key parameters of polymersome formulations. Regulatory authorities have provided valuable insights on critical quality attributes of liposomes in their guidance document on liposomal nanosimilars. Inspired by this guidance document, this Perspective proposes necessary characterization of polymersomes (hallmarks) regarding their chemical composition, physicochemical properties, drug release profile, stability, stimuli responsiveness, and pharmacokinetics and biodistribution.

Extracellular vesicles (EVs) are secreted by most cell types and play a central role in cell-cell communication. These naturally occurring nanoparticles have been particularly implicated in cancer, but EV heterogeneity and lengthy isolation methods with low yield make them difficult to study. To circumvent the challenges in EV research, we aimed to develop a unique synthetic model by engineering bioinspired liposomes to study EV properties and their impact on cellular uptake. We produced EV-like liposomes mimicking the physicochemical properties as cancer EVs. First, using a panel of cancer and non-cancer cell lines, small EVs were isolated by ultracentrifugation and characterized by dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Cancer EVs ranged in mean size from 107.9 to 161 nm by NTA, hydrodynamic diameter from 152 to 355 nm by DLS, with a zeta potential ranging from - 25 to -6 mV. EV markers TSG101 and CD81 were positive on all EVs. Using a microfluidics bottom-up approach, liposomes were produced using the nanoprecipitation method adapted to micromixers developed by our group. A library of liposome formulations was created that mimicked the ranges of size (90-222 nm) and zeta potential (anionic [-47 mV] to neutral [-1 mV]) at a production throughput of up to 41 mL/h and yielding a concentration of 1 × 1012 particles per mL. EV size and zeta potential were reproduced by controlling the flow conditions and lipid composition set by a statistical model based on the response surface methodology. The model was fairly accurate with an R-squared > 70% for both parameters between the targeted EV and the obtained liposomes. Finally, the internalization of fluorescently labeled EV-like liposomes was assessed by confocal microscopy and flow cytometry, and correlated with decreasing liposome size and less negative zeta potential, providing insights into the effects of key EV physicochemical properties. Our data demonstrated that liposomes can be used as a powerful synthetic model of EVs. By mimicking cancer cell-derived EV properties, the effects on cellular internalization can be assessed individually and in combination. Taken together, we present a novel system that can accelerate research on the effects of EVs in cancer models.

The immunosuppressive tumor microenvironment (TME) plays a crucial role in the progression and treatment resistance of melanoma. Modulating the TME is thus a key strategy for enhancing therapeutic outcomes. Previousstudies have identified clonidine (CLD), an α2-adrenergic receptor agonist, as a promising agent that enhances T lymphocyte infiltration and reduces myeloid-derived suppressor cells within the TME, thereby promoting antitumor immune responses. In this study, we discovered that CLD reshaped the melanoma immune microenvironment, facilitating T-cell activation and exerting antitumor effects. However, the high doses of CLD required for effective TME modulation pose significant toxicity concerns, limiting its clinical applicability. To address this, we employed the controllable cavitation-on-a-chip (CCC) platform to formulate CLD-loaded liposomes and optimize their size. This approach aimed to enhance the precision and efficacy of drug delivery while reducing systemic side effects. Our results demonstrated that size-specific CLD liposomes, particularly those at 50 nm, significantly improved tumor growth inhibition and immune cell infiltration within the TME. Moreover, these optimized liposomes mitigate adverse effects associated with high-dose CLD treatment. This study indicates the potential of CCC-optimized CLD liposomes as a safer and more effective melanoma therapy, highlighting the critical interplay between liposome size control and therapeutic outcomes in cancer treatment.

Lipid-mediated delivery of active pharmaceutical ingredients (API) opened new possibilities in advanced therapies. By encapsulating an API into a lipid nanocarrier (LNC), one can safely deliver APIs not soluble in water, those with otherwise strong adverse effects, or very fragile ones such as nucleic acids. However, for the rational design of LNCs, a detailed understanding of the composition-structure-function relationships is missing. This review presents currently available computational methods for LNC investigation, screening, and design. The state-of-the-art physics-based approaches are described, with the focus on molecular dynamics simulations in all-atom and coarse-grained resolution. Their strengths and weaknesses are discussed, highlighting the aspects necessary for obtaining reliable results in the simulations. Furthermore, a machine learning, i.e., data-based learning, approach to the design of lipid-mediated API delivery is introduced. The data produced by the experimental and theoretical approaches provide valuable insights. Processing these data can help optimize the design of LNCs for better performance. In the final section of this Review, state-of-the-art of computer simulations of LNCs are reviewed, specifically addressing the compatibility of experimental and computational insights.

Epilepsy is a common neurological disease characterized by distinct pathological changes in the epileptogenic zone. Antiseizure drugs (ASDs) are widely used as the primary treatment for epilepsy. To improve the efficiency of ASDs medication, stimuli-responsive nanoscale drug delivery systems (nanoDDSs), triggered by either endogenous or exogenous factors, have been developed and been considered as a noninvasive and spatial-temporal approach to epilepsy theranostics. In this review, we introduce the pathological variations observed in epileptic lesions such as dysregulated neurotransmitter systems, disrupted ion homeostasis, and dynamic inflammatory cytokine networks. Furthermore, we summarize the recent advances in functional nano-assemblies that could be activated by endogenous stimuli of pathological alterations or exogenous stimuli such as electricity, light, and other interventions. Finally, we discuss the remaining challenges and prospect the insight into perspective of future development in this field. In summary, this review aims to highlight the potential of stimuli-responsive nanoDDSs as precise, controllable and efficient strategies for addressing unresolved issues in epilepsy theranostics. STATEMENT OF SIGNIFICANCE: This review summarizes recent progress in pathological changes such as dysregulated neurotransmitter system, disrupted ion homeostasis and dynamic inflammatory cytokine network, and emphasizes endogenous/exogenous stimuli-responsive nanoscale platforms including neurotransmitter-, ion-, and other stimuli-responsive nanoDDSs, providing the prospects of smart nanoDDSs applications and discussing the challenges to offer generalized guideline for further development of epilepsy theranostics.

Drospirenone (DROP) is a highly effective, low-toxicity, safe new generation progestin that counteracts estrogen-related sodium retention, is well tolerated, and has a positive effect on premenstrual syndrome (PMS). However, the low water solubility of DROP and its chemical instability resulted in low bioavailability. In this study, we developed a two-step delivery system to enhance drospirenone's solubility and stability. We prepared a drospirenone liposome complex to optimize the encapsulation process and achieve an encapsulation efficiency of (84.9 ± 0.73) %, with an 878-fold increase in solubility under optimal conditions. To address the instability of high drug-loading liposomes, we immobilized the drospirenone liposome inclusion complex using a cellulose-based hydrogel. The system achieved uniform loading of liposomes in the hydrogel, as confirmed by SEM and FTIR analysis. 0.5 g hydrogel can be loaded with up to 96.48 mg drospirenone, and the encapsulation efficiency is (80.4 ± 1.17%). It was indicating the potential for wider application of drospirenone with enhanced water solubility and improved stability. At the same time, it also provides support for sustained-release systems or large dose drug delivery.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease primarily affecting elderly individuals aged >65 years and has a poor prognosis. No effective treatment is currently available for IPF. The two antipulmonary fibrosis drugs nintedanib and pirfenidone approved by the FDA in the United States have somewhat decelerated IPF progression. However, the side effects of these drugs can lead to poor patient tolerance and compliance with the medications. Researchers have recently developed various methods for IPF treatment, such as gene silencing and pathway inhibitors, which hold great promise in IPF treatment. Nevertheless, the nonselectivity and nonspecificity of drugs often affect their efficacies. Drug delivery systems (DDS) are crucial for delivering drugs to specific target tissues or cells, thereby minimizing potential side effects, enhancing drug bioavailability, and reducing lung deposition. This review comprehensively summarizes the current state of DDS and various delivery strategies for IPF treatment (e.g., nano-delivery, hydrogel delivery, and biological carrier delivery) to completely expound the delivery mechanisms of different drug delivery carriers. Subsequently, the advantages and disadvantages of different DDS are fully discussed. Finally, the challenges and difficulties associated with the use of different DDS are addressed so as to accelerate their rapid clinical translation.

Lipid nanoparticles (LNPs) for nucleic acid delivery often use novel lipids as functional excipients to modulate the biodistribution, pharmacokinetics, pharmacodynamics and efficacy of the nucleic acid. Novel excipients used in pharmaceutical products are subject to heightened regulatory scrutiny and often require data packages comparable to an active pharmaceutical ingredient. Although these regulatory requirements may help to ensure patient safety they also create economic and procedural barriers that can disincentivize innovation and delay clinical investigation. Despite the unique structural and functional role of lipid excipients in LNPs, there is limited specific global regulatory guidance, which adds uncertainty and risk to the development of LNPs. In this Perspective we provide an industry view on the chemistry, manufacturing and controls challenges that pharmaceutical companies face in the use of novel lipid excipients at each stage of development, and propose consensus recommendations on how to streamline and clarify development and regulatory expectations.

The incidence and mortality rates of liver cancer in China remain elevated. Although early-stage liver cancer is amenable to surgical resection, a significant proportion of patients are diagnosed at advanced stages. Currently, in addition to surgical resection for hepatocellular carcinoma, the primary treatment modalities predominantly include chemotherapy. The widespread use of chemotherapy, which non-selectively targets both malignant and healthy cells, often results in substantial immunosuppression. Simultaneously, the accumulation of chemotherapeutic agents can readily induce drug resistance upon reaching the physiological threshold, thereby diminishing the efficacy of these treatments. Besides chemotherapy, there exist targeted therapy, immunotherapy and other therapeutic approaches. Nevertheless, the development of drug resistance remains an inevitable challenge. To address these challenges, we turn to nanomedicine, an emerging and widely utilized discipline that significantly influences medical imaging, antimicrobial strategies, drug delivery systems, and other related areas. Stable and safe nanomaterials serve as effective carriers for delivering anticancer drugs. They enhance the precision of drug targeting, improve bioavailability, and minimize damage to healthy cells. This review focuses on common nanomaterial carriers used in hepatocellular carcinoma (HCC) treatment over the past five years. The following is a summary of the three drugs: Sorafenib, Gefitinib, and lenvatinib. Each drug employs distinct nanomaterial delivery systems, which result in varying levels of bioavailability, drug release rates, and therapeutic efficacy.

The integration of microbiome research and nanotechnology represents a significant advancement in immuno-oncology, potentially improving the effectiveness of cancer immunotherapies. Recent studies highlight the influential role of the human microbiome in modulating immune responses, presenting new opportunities to enhance immune checkpoint inhibitors (ICIs) and other cancer therapies. Nanotechnology offers precise drug delivery and immune modulation capabilities, minimizing off-target effects while maximizing therapeutic outcomes. This review consolidates current knowledge on the interactions between the microbiome and the immune system, emphasizing the microbiome's impact on ICIs, and explores the incorporation of nanotechnology in cancer treatment strategies. Additionally, it provides a forward-looking perspective on the synergistic potential of microbiome modulation and nanotechnology to overcome existing challenges in immuno-oncology. This integrated approach may enhance the personalization and effectiveness of next-generation cancer treatments, paving the way for transformative patient care.

Pancreatic cancer is a malignant tumor with one of the worst prognoses among solid tumors, characterized by resistance to treatment. Therefore, there is an urgent need for new methods of targeted therapy. Previous studies have shown that the overexpression of receptor tyrosine kinases such as c-KIT or PDGFR can increase proliferation, migration, and invasion of cancer cells. The aim of our study was to analyze aggregates between a supramolecular carrier (Congo red, CR) and a tyrosine kinase inhibitor (BLU-258) as well as to investigate the effect of the free inhibitor and its aggregate with Congo red (CR-BLU-258) on selected properties of pancreatic cells, including these cells' viability and three-dimensional cell spheroid cultures. To better understand the interactions between Congo red and BLU-258, we used molecular modeling in addition to biophysical methods. These attempts allowed us to determine the optimal molar ratio, which we used for in vitro studies on pancreatic cancer cell lines. A significantly greater decrease in the viability of the tested 3D cultures was observed after 48 h of incubation with CR-BLU-258, which resulted in a lower IC50 value for the tested co-aggregate compared with BLU-258 alone. Moreover, a higher resistance of PANC-1 and BxPC3 spheroid cells to the tested compounds was noted compared with the 2D culture model. A significantly lower response was observed in 3D cell cultures (BxPC3 and PANC-1) treated with BLU-258 alone compared with the 2D culture. Thus, our results showed that both BLU-258 (alone) and in its co-aggregate with Congo red exhibit anticancer activity, inhibiting the growth of pancreatic cancer cells and reducing their viability, survival, and migration. Both tested compounds also affected the phosphorylation of the selected signaling proteins. We conclude that the selected tyrosine kinase inhibitor (alone) and in its co-aggregate with Congo red exhibit anticancer activity and should be considered as a novel effective therapy against pancreatic cancer.

Liposomes are widely recognized as effective drug delivery systems, characterized by biodegradability, biocompatibility, and ability to minimize toxicity. However, liposome-based nanotechnology has not demonstrated superior anti-tumor efficacy due to their limited intratumor penetration. Strategies to improve the tumor delivery efficiency of nanomedicine remain to be developed. Moreover, the specific steps involving inter-/intra-cellular pathways in delivery could not be fully revealed by real experiment. Mathematical modeling is a great choice. Hence, this study analyzed the roles of physicochemical properties of liposomes and tumorassociated environment in intratumoral penetration, using ten anti-tumor liposomes datasets to develop two kinetic models in tumor spheroid cells based on transcytosis and paracellular transport mechanisms. Modeling results reveal the dominated penetration pathway of liposomes studied through the paracellular pathway compared to transcytosis. Liposomes with positive surface charge and high membrane fluidity enhance the maximal binding capacity on the cell membrane. Smaller liposome sizes promote internalization on the cell membrane, leading to increased drug accumulation within the cell. The pattern of liposome penetration remained consistent across different tumor-associated environments. Our developed kinetic models accurately described the penetration process of liposomes in multicellular tumor spheroid, offering valuable insights for the development of new nano antitumor medications with similar characteristics from a pharmacokinetic perspective at the tissue level.

Extracellular vesicles (EVs) are endogenous vesicles secreted by cells. Exosomes (30-150 nm), are a subset of EVs playing key roles in intercellular communication. Exosomes show promise as cancer chemotherapeutic drug delivery vehicles given their low immunogenicity and cell-specific cytosolic delivery of their contents. However, inefficient drug loading limits their therapeutic application. To address this, methods for the fusion of EVs with therapeutic drug-loaded synthetic liposomes have been developed. While more efficient than passive incubation of EVs with liposomes, these risk either damage to EV membrane proteins or contamination of the EV-liposome hybrids with residual depletant molecules, which can cause side effects or hinder content delivery. Here, we present a new, weakly perturbative method, which uses acidic conditions (pH 5) to enhance the fusion of EVs and synthetic, neutral liposomes (NLs) compared to passive incubation in pH 7.4 at 37 °C. An adapted Forster resonance energy transfer (FRET) based lipid mixing assay confirms that fusion is enhanced with this method, albeit less efficiently than with depletant-induced fusion. This significant finding implies that lipid-only synthetic liposomes can fuse with EVs, creating EV-liposome hybrids under relevant temperature and pH conditions, without nonlipidic components, such as fusogenic amphipathic peptides, added to the synthetic liposomes. Remarkably, differential interference contrast (DIC) and fluorescence microscopy show that this enhanced fusion corresponds with the clustering of mixtures of EVs and NLs, or EVs alone, in acidic but not neutral pH conditions. The findings support a hypothesis that content release from EVs in early to late endocytic environments may be a combination of protein-protein clustering interactions and a lipidic component. Further, this study provides a novel method for enhanced fusion of EVs and liposomes, which is expected to preserve EV membrane proteins and functionality toward the development of therapeutic hybrid drug delivery vehicles in nanomedicine applications.

The tumor microenvironment, with its complex immune evasion mechanisms, significantly hinders the efficacy of anti-tumor immunotherapies, including immune checkpoint inhibitors. Consequently, there is a strong impetus for extensive research to elucidate the immunosuppressive mechanisms within the tumor microenvironment and to develop novel therapeutic strategies. In this study, we have developed a drug/gene delivery system (folate-modified GW4869-loaded siIRF3 nano-complex, FD9R-GW/siIRF3) designed to simultaneously target and inhibit two key immune evasion pathways in the tumor microenvironment. The folate receptor-mediated delivery of GW4869 to cancer cells and tumor-associated macrophages (TAMs) led to the suppression of biosynthesis and release of tumor-derived exosomes (TEXs) containing exosomal PD-L1. Furthermore, IRF3 gene silencing effectively inhibited the M2-type differentiation of TAMs, and suppressed the secretion of CC motif chemokine ligand 22 (CCL22) in cancer cells, consequently reducing the recruitment of regulatory T cells (Tregs). The efficacy of FD9R-GW/siIRF3 in impeding tumor immune evasion was substantiated by an augmented recruitment of cytotoxic T cells and a diminished M2 macrophage polarization in the folate receptor-expressing 4 T1 allograft breast cancer model. Furthermore, the combination of a-PD-1 immunotherapy with FD9R-GW/siIRF3 led to a significant enhancement in the antitumor immune response, as evidenced by the inhibition of circulating tumor-derived exosomal PD-L1.

Acoustic tweezers are a highly promising technology for targeted drug delivery thanks to their unique capabilities: (i) they can effectively operate in both in vitro and in vivo environments, (ii) they can manipulate a wide range of particle sizes and materials, and (iii) they can exert forces several orders of magnitude larger than competing techniques while remaining safe for biological tissues. In particular, tweezers capable of selectively capturing and manipulating objects in 3D with a single beam, known as 'single beam tweezers', open new perspectives for delivering drug carriers to precise locations. In this review, we first introduce the fundamental physical principles underlying the manipulation of particles using acoustic tweezers and highlight the latest advancements in the field. We then discuss essential considerations for the design of drug delivery carriers suitable for use with acoustic tweezers. Finally, we summarise recent promising studies that explore the use of acoustic tweezers for in vitro, ex vivo, and in vivo drug delivery.

Platelet-derived microvesicles (PMVs) and their encapsulated microRNAs (miRNAs) hold immense potential as biomarkers for early non-small cell lung cancer (NSCLC) diagnosis. This study presents a pioneering liposome-based approach for enhanced miRNA detection within PMVs, employing a lambda exonuclease (λ EXO)-based amplification system encapsulated in immunoliposomes. The platform exploits the novel catalytic functionality of λ EXO, demonstrating its unprecedented capability to catalyze RNA-DNA hybrid substrates. The λ EXO-based amplification system exhibited high sensitivity and specificity in detecting miRNA-21, a key miRNA associated with NSCLC, demonstrating a limit of detection (LOD) of 33.11 fg mL-1. The system was successfully encapsulated within liposomes, which were then functionalized with CD41 antibody to facilitate targeted delivery and fusion with PMVs. The results reveal a significant difference in miRNA-21 levels between PMVs from NSCLC patients and healthy individuals, with a 2.06-fold higher abundance observed in NSCLC patients. This research presents a significant technological advancement in miRNA detection, paving the way for improved early diagnosis and personalized medicine approaches.

Recent advancements in cancer therapy have highlighted the dual role of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in both cell cycle regulation and immune activation. However, applying CDK4/6i to immunologically unfavorable tumors is challenging due to the complex tumor microenvironment (TME), characterized by inadequate T cell recruitment and exclusion mechanisms that hinder an effective antitumor immunity. In this work, we iteratively designed prodrug liposomal nanocarriers that integrate multiple functions: cell cycle inhibition through encapsulation of CDK4/6i, immune activation via concurrent delivery of an oral gavage-inducing chemotherapy agent, and overcoming T cell exclusion through the incorporation of a cholesterol prodrug. This iterative nanocarrier design effectively improves the pharmacokinetic profile of CDK4/6i, overcomes the immunosuppressive TME, achieves superior antitumor efficacy, and synergizes with immune checkpoint inhibitors to provide lasting effects in various colon cancer animal models.

We report the development of a nanotechnology to co-deliver chemocoxib A with a reactive oxygen species (ROS)-activatable and COX-2 targeted pro-fluorescent probe, fluorocoxib Q (FQ) enabling real time visualization of COX-2 and CA drug delivery into solid cancers, using a di-block PPS 135 - b -POEGA 17 copolymer, selected for its intrinsic responsiveness to elevated reactive oxygen species (ROS), a key trait of the tumor microenvironment. FQ and CA were synthesized independently, then co-encapsulated within micellar PPS 135 - b -POEGA 17 co-polymeric nanoparticles (FQ-CA-NPs), and were assessed for cargo concentration, hydrodynamic diameter, zeta potential, and ROS-dependent cargo release. The uptake of FQ-CA-NPs in mouse mammary cancer cells and cargo release was assessed by fluorescence microscopy. Intravenous delivery of FQ-CA-NPs to mice harboring orthotopic mammary tumors, followed by vital optimal imaging, was used to assess delivery to tumors in vivo . The CA-FQ-NPs exhibited a hydrodynamic diameter of 109.2 ± 4.1 nm and a zeta potential (ζ) of -1.59 ± 0.3 mV. Fluorescence microscopy showed ROS-dependent cargo release by FQ-CA-NPs in 4T1 cells, decreasing growth of 4T1 breast cancer cells, but not affecting growth of primary human mammary epithelial cells (HMECs). NP-derived fluorescence was detected in mammary tumors, but not in healthy organs. Tumor LC-MS/MS analysis identified both CA (2.38 nmol/g tumor tissue) and FQ (0.115 nmol/g tumor tissue), confirming the FQ-mediated image guidance of CA delivery in solid tumors. Thus, co-encapsulation of FQ and CA into micellar nanoparticles (FQ-CA-NPs) enabled ROS-sensitive drug release and COX-2-targeted visualization of solid tumors.

Muscle regeneration is a vital biological process that is crucial for maintaining muscle function and integrity, particularly for the treatment of muscle diseases such as sarcopenia and muscular dystrophy. Generally, muscular tissues can self-repair and regenerate under various conditions, including acute or chronic injuries, aging, and genetic mutation. However, regeneration becomes challenging beyond a certain threshold, particularly in severe muscle injuries or progressive diseases. In recent years, liposome-based nanotechnologies have shown potential as promising therapeutic strategies for muscle regeneration. Liposomes offer an adaptable platform for targeted drug delivery due to their cell membrane-like structure and excellent biocompatibility. They can enhance drug solubility, stability, and targeted delivery while minimizing systemic side effects by different mechanisms. This review summarizes recent advancements, discusses current applications and mechanisms, and highlights challenges and future directions for possible clinical translation of liposome-based nanomaterials in the treatment of muscle diseases. It is hoped this review offers new insights into the development of liposome-enabled nanomedicine to address current limitations.

Liposome-based targeted drug delivery systems represent a significant advancement in pharmaceutical science, offering distinct advantages that enhance the efficacy and safety of various therapies. These versatile carriers can encapsulate both hydrophilic and hydrophobic drugs, making them particularly valuable in clinical settings. This review explores the critical role of liposomal formulations in improving drug pharmacokinetics and minimizing side effects, especially in oncology, where targeted delivery to tumor cells is essential. Outlining the properties of different types of liposomes, we focus on the effects of these properties on the liposomes' targeting and drug release capabilities through innovative surface modifications and describe the most common methods of liposome preparation and characterization. Furthermore, this review provides an in-depth analysis of the properties and composition of liposomal-based nanocarriers, with a unique focus on ongoing clinical trials and recently approved therapies. It offers a comprehensive overview of the latest advancements in pre-clinical research and highlights the critical progress in clinical development, offering insights into the clinical impact and regulatory approvals. Ultimately, this review underscores the transformative potential of liposomal nanocarriers in modern therapeutics, suggesting avenues for future innovations and clinical breakthroughs.

Colon cancer remains a significant global health challenge; however, the treatment outcome for colon patients can be improved through early detection and effective treatment. Nano-radiopharmaceuticals, combining nanotechnology with radiopharmaceuticals, are emerging as a revolutionary approach in both colon cancer diagnostic imaging and therapy, playing a significant role in the management of colon cancer patients. This review examines the use of nano-radiopharmaceuticals in the diagnosis and treatment of colon cancer, highlighting current applications, challenges, and future directions. Nanocarriers of radionuclides have shown potential in improving cancer treatment, including liposomes, microparticles, nanoparticles, micelles, dendrimers, and hydrogels, which are approved by the FDA. These nanocarriers can deliver targeted drugs into malignant cells without affecting normal cells, reducing side effects. Antibody-guided systemic radionuclide-targeted therapy has shown potential for treating cancer. Novel cancer nanomedicines, like Hensify and 32P BioSilicon, are under clinical development for targeted radiation delivery in percutaneous intratumoral injections. Although using nano-radiopharmaceuticals is a superior technique for diagnosing and treating colon cancer, there are limitations and challenges, such as the unintentional accumulation of nanoparticles in healthy tissues, which leads to toxicity due to biodistribution issues, as well as high manufacturing costs that limit their availability for patients. However, the future direction is moving toward providing more precise radiopharmaceuticals, which is crucial for enhancing the diagnosis and treatment of colon cancer and reducing production costs.

Recent advancements in nanotechnology have revolutionized cancer therapy-one of the most pressing global health challenges and a leading cause of death-through the development of liposomes (L), lipid-based nanovesicles known for their biocompatibility and ability to encapsulate both hydrophilic and lipophilic drugs. More recent innovations have led to the creation of stimuli-responsive L that release their payloads in response to specific endogenous or exogenous triggers. Dual- and multi-responsive L, which react to multiple stimuli, offer even greater precision, improving therapeutic outcomes while reducing systemic toxicity. Additionally, these smart L can adjust their physicochemical properties and morphology to enable site-specific targeting and controlled drug release, enhancing treatment efficacy while minimizing adverse effects. This review explores the latest advancements in endogenous stimuli-responsive liposomal nanocarriers, as well as dual- and multi-responsive L that integrate internal and external triggers, with a focus on their design strategies, mechanisms, and applications in cancer therapy.

Local anesthetics (LAs) have been indispensable in clinical pain management, yet their limitations, such as short duration of action and systemic toxicity, necessitate improved delivery strategies. Hydrogels, with their biocompatibility, tunable properties, and ability to modulate drug release, have been extensively explored as platforms for enhancing LA efficacy and safety. This narrative review explores the historical development of LAs, their physicochemical properties, and clinical applications, providing a foundation for understanding the integration of hydrogels in anesthetic delivery. Advances in thermoresponsive, stimuli-responsive, and multifunctional hydrogels have demonstrated significant potential in prolonging analgesia and reducing systemic exposure in preclinical studies, while early clinical findings highlight the feasibility of thermoresponsive hydrogel formulations. Despite these advancements, challenges such as burst release, mechanical instability, and regulatory considerations remain critical barriers to clinical translation. Emerging innovations, including nanocomposite hydrogels, biofunctionalized matrices, and smart materials, offer potential solutions to these limitations. Future research should focus on optimizing hydrogel formulations, expanding clinical validation, and integrating advanced fabrication technologies such as 3D printing and artificial intelligence-driven design to enhance personalized pain management. By bridging materials science and anesthetic pharmacology, this review provides a comprehensive perspective on current trends and future directions in hydrogel-based LA delivery systems.

Radiotherapy is crucial in local cancer management and needs advancements. Tumor cells elevate intracellular copper levels to promote growth and resist radiation; thus, targeted copper delivery to mitochondria could enhance radiotherapy by inducing cuproptosis in tumor cells. In this study, we engineered a multifunctional nanoliposome complex, termed Lipo-Ele@CuO2, which encapsulates both copper peroxide (CuO2) and the copper chelator elesclomol, which can delivery Cu ions to the mitochondria. The Lipo-Ele@CuO2 complex induces mitochondria-mediated cuproptosis in tumor cells and synergistically enhances the efficacy of radiotherapy. CuO2 acts as a copper donor and exhibits inherent sensitivity to acidic environments. Additionally, it depletes intracellular glutathione, thereby sensitizing cells to cuproptosis. Leveraging its pH-responsive properties in the acidic tumor microenvironment, the Lipo-Ele@CuO2 facilitate the controlled release of elesclomol, efficiently delivering copper ions to mitochondria at tumor sites. The combined in vitro and in vivo studies demonstrate that Lipo-Ele@CuO2-based therapy significantly improves antitumor efficacy and exhibits excellent safety profiles, effectively inducing cuproptosis in tumor cells and boosting the effectiveness of radiotherapy. Furthermore, metabolomic and transcriptomic analyses reveal that this combination therapy precipitates significant alterations in tumor energy metabolism, notably repressing genes related to iron-sulfur cluster assembly and glycolysis, thereby confirming the induction of cuproptosis. This therapeutic strategy provides a viable approach for addressing clinical radiotherapy resistance and demonstrates significant translational potential.

In Langmuir monolayers of heneicosanoic acid (C21H42O2), at low temperature, in the L'2 and CS crystalline phases, a blinking phenomenon occurs at the same positions of the monolayer, which is called localized oscillations (LO), but its origin has not been clarified. In this study, the LO phenomenon was correlated with the ejection of material out of the monolayer which was analyzed to understand this phenomenon. The techniques used for this purpose were pressure-area isotherms on a Langmuir balance and simultaneous observation of the monolayer by Brewster angle microscopy (BAM). Subsequently, using the Langmuir-Blodgett technique, the monolayers were transferred using freshly cleaved mica substrates for analysis by atomic force microscopy (AFM). Our results showed that the origin of the LO is related to a spontaneous formation of micelles and vesicles, since in AFM images these structures were observed in a size range from 4 to 16 nm. In addition, the AFM images showed that the difference between the heights of the L'2 and CS crystalline phases ranges from 13 to 15 Å.