International Journal of Nanomedicine最新文献

Neurological disorders, including ischemic stroke, Alzheimer's disease, and Parkinson's disease, exhibit high incidence rates and pose significant health challenges. Current pharmacological treatments often fail to adequately address clinical needs due to obstacles such as limited penetration of the blood-brain barrier and suboptimal efficacy. Plant-derived exosome-like nanoparticles (PELNs) have emerged as promising therapeutic agents due to their superior biocompatibility, low toxicity, ability to traverse the blood-brain barrier, and abundance of lipids, microRNAs, and other bioactive compounds. This review provides a comprehensive overview of recent advancements in PELNs preparation technologies, elucidates the mechanisms of action of their principal bioactive components, and explores their therapeutic applications across various neurological disorders, thereby offering a theoretical foundation for the development of related treatment strategies. Nonetheless, researches on PELNs continue to encounter significant challenges. At the production level, there is an absence of standardized isolation protocols, and the yields remain inadequate to satisfy clinical requirements. Clinically, the efficacy in humans has yet to be established, and the available safety data are insufficient. Technically, the lack of standardized storage conditions and the susceptibility of biological stability to external factors further complicate the field. This review delineates these challenges to offer insights for advancing both fundamental research and the clinical translation of PELNs.

Background: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, characterized by persistent immune dysregulation. Umbilical cord mesenchymal stem cell-derived extracellular nanovesicles (MSC NVs) exhibit immunomodulatory properties, demonstrating significant therapeutic potential for clinical applications. This study sought to investigate the therapeutic effects of MSC NVs against colitis and elucidate the underlying mechanisms.

Methods: MSC NVs were prepared from umbilical cord MSCs using a continuous filtration-extrusion method. The therapeutic effects of MSC NVs were assessed by tail vein injection in a murine model of DSS-induced colitis.

Results: MSC NVs significantly markedly ameliorated colitis-associated symptoms, including body weight loss, colon length reduction, and elevated disease activity index scores. MSC NVs not only mitigated colitis-induced intestinal barrier impairment and inflammatory responses, but also exhibited targeted biodistribution to inflamed colonic lesions. Unexpectedly, administration of MSC-NVs via the tail vein significantly altered the gut microbial composition in colitic mice, particularly enhancing the relative abundances of beneficial commensal genera Lachnoclostridium and Dubosiella, consequently reestablishing microbial homeostasis. Moreover, MSC NVs modulated the T help (Th) 17/ regulatory T (Treg) balance within the colonic lamina propria through delivery of hsa-miR-27b-3p, which directly targeted the PIK3CA gene, thereby inhibiting PI3K/AKT/STAT3 signaling pathway activation and exerting anti-colitis effects.

Conclusion: This study demonstrated that MSC NVs significantly alleviated DSS-induced colitis by modulating Th17/Treg balance in the colonic lamina propria, with hsa-miR-27b-3p identified as the key mediator through PIK3CA targeting and PI3K/AKT/STAT3 pathway inhibition. These findings highlight the therapeutic potential of filtration-extrusion-prepared MSC NVs as a safe and effective nanomedicine for IBD treatment.

Background: In the microenvironment of atherosclerosis (AS), low-density lipoprotein (LDL) accumulates in injured endothelial areas and undergoes oxidation, thereby generating oxidized LDL (ox-LDL). The formation of ox-LDL, in turn, not only amplifies endothelial cell (EC) dysfunction but also triggers macrophage polarization into the pro-inflammatory M1 phenotype. This cascade results in increased inflammatory cytokine secretion and exacerbated lipid accumulation. Therefore, a dual-targeting strategy aimed at both ECs and macrophages to inhibit the vicious circle between inflammation and lipids is a promising avenue for AS treatment.

Methods: Simvastatin (SIM)-loaded nanomicelles (PLA-PEG/SIM) were prepared using the thin-film hydration method. Then, platelet membrane (PM) was coated the nanomicelles via sonication to obtain PM@PLA-PEG/SIM dual-targeting biomimetic nanoparticles. The morphological features of the nanoparticles were assessed by transmission electron microscopy (TEM). Cytotoxicity was evaluated using the CCK-8 assay and live/dead cell staining. Their targeting ability toward ECs and macrophages was assessed by flow cytometry and confocal laser scanning microscopy (CLSM). The biosafety, targeting ability, and therapeutic efficacy of PM@PLA-PEG/SIM against AS were further validated in ApoE^-/- mouse models.

Results: PM@PLA-PEG/SIM effectively reduced the drug toxicity of SIM, exhibiting good biocompatibility. In vitro, cell experiment results showed that the nanoparticles inhibited foam cell formation, decreased interleukin-6 (IL-6) expression, and increased interleukin-4 (IL-4) and interleukin-10 (IL-10) expression by promoting macrophage repolarization. In vivo, results indicated that the formulation demonstrated excellent plaque-targeting ability. More importantly, the plaque area and lipid levels in the PM@PLA-PEG/SIM group were lowest, and plaques were most stable, showing its best therapeutic efficiency.

Conclusion: PM@PLA-PEG/SIM alleviated progression of AS by co-targeting ECs and macrophages to inhibit the vicious cycle between inflammation and lipids. Our study provides a new strategy for the treatment of the disease by the co-targeting biomimetic nanoparticle.

Objective: Itraconazole (ITZ) is a BCS class II antifungal agent difficult to formulate due to its poor water solubility (<0.2 mmol /mL) and variable oral bioavailability (~55%). This study aimed to develop Polycaprolactone (PCL) nanoparticles to improve their transdermal delivery.

Methods: The nanoparticles were prepared using a modified nanoprecipitation method, resulting in ten formulations (F1 to F10). The optimized formulation (F2) was incorporated into a carbopol gel. Characterization included particle size, polydispersity index (PDI), zeta potential, encapsulation efficiency (EE), and in vitro drug release at pH 5.5 and 7.4. Ex vivo permeation, skin irritation, and stability were also evaluated.

Results: Formulation F2 (40 mg PCL, 2% Poloxamer 407 showed optimal properties: particle size of 154.6 nm, PDI (0.378), zeta potential (-10.7 ± 5.36 mV), and EE (88.4 ± 1.2%). A pH-dependent sustained release was observed, with 80.41% and 94.34% cumulative release at pH 5.5 and 7.4 over 24 hours, respectively, following Higuchi kinetics (R²= 0.9804 at pH 5.5). The gel demonstrated significantly higher permeation (Q_{2 4}: 173.29 ± 3.12 μg/cm²; Jss: 7.22 ± 0.15 μg/cm²/h) versus plain gel (Q_{2 4}: 75.35 ± 1.35 μg/cm²; Jss: 3.11 ± 0.08 μg/cm²/h), with an enhancement ratio of 2.32. Characterization confirmed the amorphous state of ITZ and absence of interactions. The formulation was non-irritating (PII=0) and stable for three months.

Conclusion:  A promising and biocompatible PCL-based gel was successfully developed, providing an effective approach for enhanced transdermal delivery of ITZ through sustained drug release and improved skin permeability.

Metal nanoparticles possess unique properties and usage patterns compared to traditional materials owing to their distinctive structures. In recent years, their application scenarios and dosages have considerably expanded. Biosynthetic nanoparticles, particularly those derived from endophytic fungi that help host organisms in adapting to heavy metal environments, hold substantial value and potential for application. This is largely attributed to their simplicity, cost-effectiveness, and energy efficiency. The present review provides an overview of the entire process of metal nanoparticle biosynthesis by plant endophytic fungi and illustrates various scenarios of their applications in oncology treatment. In addition to focusing on the preparation of metal nanoparticles using plant endophytic fungi, this review also explores the characterization of these nanoparticles and clarifies the synthesis mechanisms, including the synthetic pathways and the roles of fungal enzymes. It also comprehensively summarizes the application of biosynthetic metal nanoparticles in cancer, covering their role in diagnosis, enhancement of drug biocompatibility, and improvement of therapeutic efficacy. These nanoparticles exhibit toxicity toward cancer cells by generating reactive oxygen species and inducing oxidative stress, ultimately leading to the death of malignant cells. The biosynthesis of metal nanoparticles by plant endophytic fungi represents a promising, green, and environmentally friendly approach with potential applications in various fields, including cancer treatment, in the future.

Amidst escalating global health challenges, neoplastic diseases remain a predominant cause of morbidity and mortality, exerting complex and far-reaching effects on human health and societal well-being. The advent of precision medicine has ushered in an era of tailored therapeutic strategies, leveraging individual genetic profiles, tumor microenvironmental features, and exogenous factors to redefine oncology care. Central to these advances is the understanding of cell death, a fundamental biological process encompassing both programmed and non-programmed forms. Programmed cell death is orchestrated through sophisticated genetic and molecular mechanisms. Emerging evidence underscores the role of metal ion dyshomeostasis, particularly of iron, copper, zinc, sodium, magnesium, manganese, and calcium, in disrupting intracellular signaling and metabolic equilibrium, thereby inducing lethal cascades in malignant cells. Concurrently, innovations in nanomedicine have enabled precise modulation of ion fluxes within tumors, enhancing therapeutic specificity while minimizing systemic toxicity. This confluence of ion-mediated cell death mechanisms and nanotechnology not only exemplifies a transformative approach in cancer treatment but also aligns seamlessly with the tenets of precision medicine, offering novel pathways for therapeutic innovation and clinical translation.

Plant-derived exosome-like nanovesicles (PELNs) are naturally derived lipid-bilayer nanocarriers, which possess intrinsic activity to modulate oxidative stress through their diverse cargos of proteins, lipids, nucleic acids, and phytochemicals. Unlike conventional oxidative-stress interventions, PELNs achieve multifactorial, cargo-based redox regulation within a protective membrane that enhances bioavailability, preserves labile components, and improves cellular uptake while reducing off-target toxicity. Their low immunogenicity and inherent stability, together with the potential for surface modification and therapeutic co-loading, enable tissue-selective and sustained control of redox balance, including integration with biomaterial platforms such as hydrogels and scaffolds. This review synthesizes advances in PELN biogenesis, compositional characteristics, and isolation methods, and compares their biological and functional traits with mammalian exosomes. We propose an antioxidant/pro-oxidant dichotomy as a unifying mechanistic framework and highlight therapeutic prospects in oxidative stress-related disorders such as wound healing, atherosclerosis, neurodegeneration, and cancer. Translational considerations-including manufacturing scale-up, stability, biodistribution and biosafety-are critically discussed, alongside practical strategies to address these challenges. By linking mechanistic understanding with material-based engineering and application-oriented perspectives, this review establishes a materials-to-clinic roadmap for PELNs and positions them as promising next-generation nano-tools for precision oxidative-stress therapy.

Introduction: The xanthophyll carotenoid astaxanthin is well-known for its potent antioxidant properties, which are superior to those of other antioxidants such as vitamins C and E. However, this highly hydrophobic compound has low solubility and poor oral bioavailability, limiting its efficacy and clinical application. To address these pharmacokinetic challenges, nanostructured lipid carriers (NLC) have been proposed as potential lipid-based drug carriers for the oral delivery of astaxanthin owing to their excellent biocompatibility, stability, and efficient drug loading capacity.

Purpose: In this study, we aimed to develop an NLC using cocoa butter and palm oil for astaxanthin encapsulation, and to optimize the nanoformulation by employing Response Surface Methodology (RSM), a statistical approach.

Methods: Three-factor Central Composite Design (CCD) in RSM was used to understand the effect of independent variables on response variables. The size, polydispersity index, and encapsulation efficiency of the astaxanthin-loaded NLC were also characterized.

Results: Findings of this study indicated that the mass of cocoa butter, palm oil and Tween 80 influenced the particle size, polydispersity index and zeta potential of NLC. The experimental determination of NLC did not differ significantly from the predicted RSM outcomes with size, polydispersity index and zeta potential of 254.42 ± 3.91 nm, 0.38 ± 0.01 and -30.54 ± 0.85 mV, respectively. This nanoparticulate system showed an excellent astaxanthin entrapment efficiency of 99.69±0.0003%.

Conclusion: The ideal combination of each composition in the NLC formulation yielded nanoparticles with desirable particle size, polydispersity index, and zeta potential for efficient oral delivery of astaxanthin.

Background: Obesity is a global public health concern, and traditional surgical interventions such as liposuction, although effective, carry risks of trauma and complications. Non-invasive phototherapies, including photobiomodulation therapy (PBMT), photodynamic therapy (PDT), and photothermal therapy (PTT), have emerged as promising alternatives.

Methods: This narrative review synthesizes current literature on phototherapy-based fat reduction. A PubMed search was conducted using the terms ("photosensitive material" OR "photodynamic therapy" OR "photothermal" OR "photobiomodulation") AND ("lipolysis" OR "fat reduction" OR "body contour"). Of 105 studies meeting inclusion criteria, 80 were selected for detailed analysis, focusing on PBMT, PDT, and PTT in non-invasive fat reduction.

Results: PDT induces adipocyte apoptosis and tissue remodeling via ROS generated by photosensitizers; PTT applies near-infrared light to heat adipose tissue, promoting fat cell death and enhancing local metabolic activity; PBMT stimulates mitochondrial activity, accelerating lipolysis and metabolic processes. Some studies indicate that the use of nanomaterials may modestly enhance targeting and therapeutic efficacy.

Conclusion: Non-invasive phototherapy shows great potential in obesity management, and the integration of nanomaterials may further enhance targeting and therapeutic efficacy, enabling safer and more efficient fat reduction. Future studies should optimize phototherapy parameters and explore the synergistic effects of nanomaterials and personalized intervention strategies.

Background and aims: Abdominal aortic aneurysm (AAA) is a vascular condition with high mortality for which no pharmacological treatments have been approved. Targeting endothelial dysfunction as a primary disease initiator, the vascular endothelial cell (VEC)- protective compound Senkyunolide I (SEI) demonstrates therapeutic promise through robust antiapoptotic activity. Nevertheless, SEI's clinical translation faces limitations due to systemic toxicity, necessitating development of safer therapeutic alternatives.

Results: This study presents an engineered biomimetic nanoplatform (Lipo-MM nanoparticles) combining macrophage-derived membranes with synthetic lipid bilayers for targeted SEI delivery. The macrophage membrane component facilitates precise targeting of activated VECs, while optimized artificial membrane fluidity enhances nanoparticle stability. This dual-membrane configuration enables sustained SEI release with enhanced biodistribution, achieving superior cytoprotective effects. Notably, we established a novel fusion membrane delivery system (Lipo-MM/SEI) and validated its therapeutic efficacy in angiotensin II-challenged AAA murine models. The nanocarrier significantly attenuated AAA progression, reflected by decreased 40% of AAA incidence, 31.4% of maximum aortic diameter, reduced elastin degradation and prevented fatal rupture events. Furthermore, Lipo-MM/SEI administration substantially reduced hepatorenal toxicity associated with free SEI administration during chronic treatment.

Conclusion: These results demonstrate that hybrid biomimetic systems integrating natural cellular components with engineered materials offer a strategic approach for vascular endothelial repair therapy while minimizing off-target effects. This membrane fusion technology establishes a prototype for developing next-generation targeted vascular therapeutics.