International Journal of Nanomedicine最新文献

Chronic wounds pose a significant and growing global health challenge, affecting millions of individuals and often leading to prolonged suffering and increased healthcare costs. A major barrier to effective healing is wound infection, which disrupts the natural repair process and contributes to the chronicity. Therefore, innovative strategies for infection control are urgently required. Deep Eutectic Solvents (DESs) have recently gained attention as promising drug delivery systems owing to their multifunctional properties. In addition to serving as penetration enhancers that improve drug permeation, DESs exhibit intrinsic antimicrobial and antibiofilm activities, making them attractive candidates for managing infected wounds. This review highlights the fundamentals of DESs in the context of chronic wound management. It provides an overview of the wound healing process, pathophysiology of chronic wounds, and the role of biofilms in persistent infections. It further explores the dual role of DESs as penetration enhancers and antibiofilm agents, summarizing the recent DES-based formulations under investigation. Finally, this review discusses the current challenges and future prospects of integrating DESs into clinical practice. Collectively, DESs represent novel and versatile therapeutic platforms that have the potential to transform the treatment landscape of chronic wound healing.

Cancer vaccines are promising, but clinical translation is constrained by inefficient antigen delivery and suboptimal immune activation. Lipid nanoparticles (LNPs)-validated for potency and safety in COVID-19 mRNA vaccines-offer a versatile, scalable, and immunogenic platform. Key barriers persist: precise targeting of tumors or lymphoid tissues, efficient intracellular mRNA release, and the immunosuppressive tumor microenvironment. This review synthesizes design principles for mRNA-loaded LNPs, emphasizing lipid chemistry, organ-selective biodistribution, and nano-engineering strategies that strengthen antigen presentation and T-cell priming. We also examine combination approaches with checkpoint blockade, chemotherapy-induced immunogenic cell death, and molecular adjuvants. Clinically, signals of efficacy are emerging-most notably the KEYNOTE-942 study, in which mRNA-4157 combined with pembrolizumab showed a sustained improvement in recurrence-free survival at 5 years compared with pembrolizumab alone-highlighting both the potential and the remaining questions for this modality. Finally, we outline manufacturing and regulatory considerations and map future directions-including thermostable formulations, self-amplifying RNA, and AI-guided lipid discovery-to address translational bottlenecks and expand global access to LNP-based cancer vaccines.

[This corrects the article DOI: 10.2147/IJN.S313093.].

Epigenetic modifications regulate gene expression at the transcriptional level, contributing to tumorigenesis and progression. While epigenetic-targeted combination therapies have gained prominence in oncology treatment management, their clinical efficacy remains constrained by differences in pharmacokinetics and biodistribution among combined agents. Nano-drug delivery systems (NDDS) demonstrate unique potential through co-delivery of therapeutic agents and optimization of their pharmacokinetic profiles. Furthermore, the development of multifunctional NDDS opens new possibilities for precision modulation in cancer treatment, offering valuable insights for clinical translation. Here, this review first outlined the intervention mechanisms of epigenetic dysregulation and analyzed the applications of epigenetic combination approaches. Subsequently, we highlight the transformative potential of NDDS in epigenetic combination therapy, with particular emphasis on how multifunctional NDDS design enables precise therapeutic regulation. This comprehensive analysis aims to advance the clinical translation of epigenetic-based combination strategies through innovative drug delivery solutions. In the future, with the continuous development of AI-driven NDDS design, biomimetic carriers, and dynamic epigenetic editing tools, it will be possible to overcome the clinical challenges of NDDS, enabling truly personalized cancer treatment.

Background: Extracellular vesicles derived from mesenchymal stem cells (MSCs-EVs) are nano-sized vesicles and have become key mediators in tissue engineering and emerging therapeutic agents in regenerative medicine. This study systematically assessed the global research trend of MSCs-EVs for tissue engineering through bibliometric analysis of literature from 2014 to 2024.

Methods: A comprehensive search of Web of Science retrieved 752 eligible articles. We visualized and further analyzed collaboration, co-citation, co-authorship and co-occurrence through VOSviewer and Citespace, focusing on their application and future development trends.

Results: Annual publications increased continuously, with China and the United States accounting for 48.9% and 19.1% of research output, respectively, accompanied by intensive transnational cooperation. China leads in number of publications, number of years, total citations, H index and collaboration. The evolution of research trends confirms that the current field of application has expanded from cellular repair to drug delivery systems and biomaterial integration. Keyword cooccurrence reveals three clusters of research: artificial editing of exosomes (membranes), drug delivery (drugs, nucleic acids), and regeneration mechanisms (bone morphogenesis, angiogenesis regulation). The International Journal of Molecular Science became the most influential journal, and Shanghai Jiaotong University was a leader in institutional productivity.

Conclusion: This study is the first comprehensive quantitative analysis of tissue-engineered EVs and details trends and advances in tissue-engineered EVs research within the field of regenerative medicine. It portrays recent frontiers and hotspots, providing valuable insights for researchers in this particular area of research.

Introduction: Metabolic dysfunction-associated steatotic liver disease has limited treatment options, posing a serious global health challenge. Epicatechin (EC), a natural flavonoid, exhibits therapeutic potential; however, its clinical utility is hindered by its low solubility and limited bioavailability. Therefore, in this study, we developed liver-targeted EC-loaded galactosylated poly(lactic-co-glycolic acid)-polyethylene glycol nanoparticles (EC@PLGA-PEG-GAL NPs) with high therapeutic efficacy.

Methods: EC@PLGA-PEG-GAL NPs were synthesized, and their physicochemical properties, biocompatibility, and hepatocyte-targeted cellular uptake were characterized. The therapeutic efficacy of the NPs was assessed in high-fat diet (HFD)-fed mice, evaluating metabolic dysfunction and hepatic steatosis. Mechanistic studies were performed to investigate the effects on autophagic flux and mitochondrial function.

Results: The EC@PLGA-PEG-GAL NPs exhibited improved EC solubility, sustained drug release, and low cytotoxicity. In HFD-fed mice, administration of EC@PLGA-PEG-GAL NPs significantly ameliorated hepatic steatosis, reduced insulin resistance, and alleviated metabolic dysfunction, without causing toxicity. Mechanistically, these NPs restored the autophagic flux by activating the AMP-activated protein kinase pathway and inhibiting mechanistic target of rapamycin complex 1 signaling, thereby enhancing ubiquitinated protein clearance. They also alleviated mitochondrial dysfunction by enhancing the membrane potential, reducing the reactive oxygen species levels, and promoting mitochondrial biogenesis.

Conclusion: Our findings highlight EC@PLGA-PEG-GAL NPs as promising liver-targeted nanotherapeutics simultaneously modulating autophagy and mitochondrial functions in metabolic dysfunction-associated steatotic liver disease.

Osteosarcoma (OS) is a malignant bone tumor primarily affecting children and teenagers, characterized by aggressiveness and early metastasis especially to the lungs. OS management is complex and combined-modality therapy involving surgery, chemotherapy and immunotherapy is common. The standard care treatment utilizing doxorubicin, cisplatin, and high-dose methotrexate is a combination ("MAP") not changed in more than 40 years that often confronts incomplete tumor removal, recurrence, drug resistance, and severe side effects. Recent advancements in nano- and precision medicine have introduced tumor-targeted drug delivery strategies through multifunctional nanocarriers which aim to enhance therapeutic efficacy by preventing rapid clearance, prolonging circulation time and improving accumulation at tumor sites while minimizing adverse effects. Although many of these smart Nanotherapeutics are still at the preclinical stage, their unique properties make their promotion in OS clinical applications a challenge. Starting from an overview of the current approved OS therapies, this review reports a systematic analysis of in vivo studies published in the last decade that employ multifunctional nanosystems, drug delivery strategies and cutting-edge technologies in chemo-, immuno- and gene therapy for OS management providing an overview of the potential and challenges of these innovative treatment strategies. Our comprehensive literature analysis points out their certain antitumoral effects in OS preclinical models; however, overcoming translational bottlenecks remains a critical challenge, as promising preclinical findings often fail to translate into effective clinical therapies. Moreover, extended long-term observation in clinical studies is still required together with an in-depth understanding of the unique genetics and biology of OS, given the complex heterogeneity of the tumor microenvironment. By analyzing the limitations of conventional therapies, the latest advancements in nanotechnology alongside key bottlenecks in clinical translation of nanotherapeutics for OS, this review provides valuable insight into future directions, particularly for combination regimens, fostering progress in OS clinical research and supporting the development of innovative and personalized therapies.

Objective: This research explored the effectiveness of RGD peptide-functionalized gold nanoparticles (AuNPs) loaded with the histone deacetylase inhibitor SAHA (suberoylanilide hydroxamic acid) to enhance the radiosensitivity of non-small cell lung cancer (NSCLC) by suppressing hypoxia signaling, thereby mitigating oxidative stress and inflammatory responses.

Methods: RGD-AuNPs-SAHA was synthesized via citrate reduction, thiol-gold bonding for RGD modification, and SAHA loading. Structural and chemical characteristics were assessed via dynamic light scattering (DLS), transmission electron microscopy (TEM), UV-Vis spectroscopy, high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS). Elemental distribution was mapped using TEM-EELS. Drug release behavior was evaluated under neutral and acidic conditions (pH 7.4 and 5.5). SAHA release kinetics were assessed at pH 7.4 and 5.5. Cellular uptake and biodistribution were evaluated in A549 cells and xenograft mice using fluorescence labeling and flow cytometry. Therapeutic efficacy was examined via tumor volume measurement, serum cytokine profiling (TNF-α, IL-6, IL-10), oxidative stress markers (SOD, CAT, MDA), and molecular analyses (IHC, IF, Western blot, RT-PCR). DNA damage and apoptosis were quantified using TUNEL and γ-H2AX staining.

Results: RGD-AuNPs-SAHA exhibited uniform size (~20 nm), high SAHA encapsulation (85.2%), and pH-responsive release (60% at pH 5.5 vs 35% at pH 7.4). XPS and EELS mapping further verified the formation of Au-S bonds between thiol-modified RGD and the AuNP surface. Quantitative analysis of surface-bound RGD peptides was performed using UV-Vis spectroscopy combined with the Levenberg-Marquardt algorithm. In vivo, RGD-AuNPs-SAHA reduced tumor volume by 60% and modulated inflammatory cytokines (↓TNF-α/IL-6, ↑IL-10). Oxidative stress markers improved significantly (SOD: 110 U/mL; CAT: 85 U/mL; MDA: ↓2 nmol/mL). Hypoxia signaling proteins HIF-1α and VEGF decreased by 50% and 40%, respectively, confirmed by Western blot and RT-PCR. Apoptosis and DNA damage markers increased by 70% (TUNEL) and 65% (γ-H2AX), demonstrating enhanced radiosensitization.

Conclusion: RGD-AuNPs-SAHA effectively remodeled the hypoxic tumor microenvironment, attenuated oxidative stress, and suppressed pro-tumorigenic signaling, leading to significant apoptosis and DNA damage. These findings highlight its potential as a radiosensitizer for NSCLC, offering a promising strategy to improve radiation therapy outcomes.

Purpose: To investigate the therapeutic potential of sulfur vacancy-molybdenum disulfide/carbon composite nanosheets (MoS_2-x/C NS) in Aspergillus fumigatus (A. fumigatus) keratitis in mice.

Methods: The in vitro antifungal efficacy of MoS_2-x/C NS against A. fumigatus was evaluated by propidium iodide (PI) staining, minimum inhibitory concentration (MIC) determination, and biofilm formation assays. Toxicity assessments of the MoS_2-x/C NS were conducted using a Lactate dehydrogenase (LDH) assay kit for in vitro cytotoxicity and the Draize eye test for in vivo ocular irritation. The severity of fungal keratitis in mice was assessed using clinical scoring, plate counting, and hematoxylin and eosin (H&E) staining. The anti-inflammatory efficacy of MoS_2-x/C NS was determined by quantifying inflammatory factor levels using reverse transcription polymerase chain reaction (RT-PCR).

Results: In vitro, MoS_{2 -x}/C NS significantly inhibited A. fumigatus growth, demonstrated favorable biocompatibility, and reduced the expression of IL-6 and TNF-α in human corneal epithelial cells (HCECs) stimulated by inactivated A. fumigatus hyphae. In vivo, MoS_{2 -x}/C NS treatment significantly reduced fungal load, attenuated pathological corneal damage, and suppressed IL-6 and TNF-α levels, effectively alleviating A. fumigatus keratitis in mice.

Conclusion: This study demonstrates that MoS_2-x/C NS possesses significant therapeutic potential for fungal keratitis mediated through dual antifungal and anti-inflammatory mechanisms, thereby improving the prognosis of A. fumigatus keratitis.

Immunotherapy is emerging as a powerful strategy against cancer; however, its efficacy is often blunted by the immunosuppressive tumor microenvironment (TME). Immunogenic cell death (ICD) can tilt this balance by releasing tumor-associated antigens and damage-associated molecular patterns that enhance TME immunogenicity, promote antigen-presenting cell maturation, and activate effector T cells. Ionizing radiation and doxorubicin (Dox) are two types of the common ICD inducers. However, they have severe off-target toxicities and limited therapeutic indices. To overcome these challenges, safe and natural products are now drawing widespread attention. Hypericin, a naturally occurring photosensitizer derived from the traditional Chinese herb Hypericum perforatum (St. John's wort), has been used medicinally for centuries, and is now recognized for its potent antimicrobial, antiviral, anti-inflammatory, and anticancer properties. Recent studies have revealed that hypericin can modulate tumor immunity, and when employed in photodynamic therapy (PDT) or sonodynamic therapy (SDT) it generates reactive oxygen species that trigger endoplasmic reticulum stress-mediated ICD. Nanocarrier-mediated delivery further amplified these effects by enhancing hypericin solubility, tumor accumulation, and ROS yield upon light irradiation. This minireview synthesizes the current knowledge on the immunomodulatory actions of hypericin within the tumor microenvironment, evaluates its performance as a PDT/SDT-based ICD inducer, and highlights that nanosized formulations of hypericin may accelerate the development of novel ICD inducers and immunomodulators.