International Journal of Nanomedicine最新文献

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.

Purpose: Doxorubicin (DOX) is a first-line chemotherapeutic agent widely recognized for its efficacy in inhibiting tumor growth. However, its clinical utility is limited by systemic toxicity, adverse side effects, and the emergence of multidrug resistance. To address these challenges, we developed a cell membrane-coated nanodrug delivery system in which DOX is loaded onto gold nanoparticles (AuNPs) via electrostatic adsorption, with the cell membrane acted as a biomimetic targeting component to improve therapeutic outcomes and reduce off-target toxicity.

Methods: The successful construction of M@DOX@AuNPs was confirmed by UV-Vis absorption spectroscopy and transmission electron microscope. Antitumor effects were evaluated through both in vitro and in vivo experiments. Biological safety was evaluated via histopathological staining and blood biochemical analysis.

Results: M@DOX@AuNPs demonstrated favorable physical stability and exhibited time-dependent drug release profiles. Cellular uptake studies revealed that M@DOX@AuNPs were internalized more efficiently in 4T1 and MDA-MB-231 cells compared to free DOX or DOX@AuNPs. Moreover, M@DOX@AuNPs significantly inhibited tumor cell viability and induced apoptosis in vitro, whereas free AuNPs or cell membranes alone showed no detrimental effects on tumor cell viability. In a mouse tumor model, M@DOX@AuNPs exhibited pronounced anti-tumor efficacy without inducing structure damage to major organs or causing significant alterations in blood cell counts and serum biochemical markers.

Conclusion: These findings indicate that M@DOX@AuNPs represent a promising targeted chemotherapeutic agent for improved tumor therapy.

Ischemic stroke (IS) poses a significant global health burden, with treatment efficacy often limited by the blood-brain barrier (BBB) and narrow therapeutic windows. Cell membrane-camouflaged biomimetic nanoparticles (CMC@NPs) represent an advanced drug delivery platform that integrates the versatility of synthetic nanocarriers with the biological functionality of natural cell membranes, thereby enhancing targeted delivery and immune evasion. However, a systematic assessment of their biosafety remains incomplete. This review critically evaluates both the safety profile and therapeutic efficacy of CMC@NPs in the context of IS, with a specific focus on the structure-activity relationships between their physicochemical properties and toxicological outcomes. We further explore their biosafety within the unique pathological microenvironment of IS. Key findings demonstrate that optimal particle size and surface functionalization critically determine biodistribution, enabling superior tissue penetration and prolonged circulation. Furthermore, naturally derived or engineered membrane proteins facilitate precise targeting to ischemic lesions, thereby enhancing drug accumulation and therapeutic efficacy. Concurrently, a mildly negative surface charge mitigates the risk of cerebral microvascular embolism, and targeted delivery significantly reduces systemic toxicity. The pivotal role of cell-specific uptake and clearance mechanisms in governing neurotoxicity and long-term accumulation is also emphasized. This review provides a foundational framework for the development of safer and more effective biomimetic nanomedicines for IS.

The demand for highly functional chemical gas sensors has surged in response to critical needs such as health monitoring, protection against harmful gases, and assessment of food freshness. Over the past few decades, various chemiresistive gas sensors have been developed, exhibiting considerable sensitivity to a range of gases. However, their performance remains constrained by notable drawbacks, including elevated operating temperatures, inadequate sensitivity, and poor selectivity. In recent years, perovskite materials have garnered substantial attention due to their exceptional chemical and physical properties-such as a high absorption coefficient, low ionic binding energy, tunable bandgap, and high carrier mobility. Concurrently, significant strides have been made in leveraging both organic and inorganic perovskite-based sensors for detecting environmental gases. This review provides a comprehensive overview of the recent advancements in perovskite-based gas sensors, systematically analyzing the field from material design and engineering to device applications. We dissect the critical influence of perovskite crystal structures and micro/nano-architectures on key performance metrics such as sensitivity, selectivity, response/recovery time, and stability. The applications of these materials in detecting a wide array of hazardous gases-including H₂S, NH₃, NOx, CO/CO₂, and various volatile organic compounds (VOCs)-are thoroughly examined, with representative examples and underlying sensing mechanisms discussed in detail. However, the path to commercialization is obstructed by persistent challenges of instability, selectivity, and the severe environmental and health risks of lead. This has catalyzed a major research thrust towards non-toxic, lead-free perovskites. Consequently, the field is pivoting towards lead-free perovskites. This analysis underscores that synergistic innovation in lead-free material science and device engineering is critical to overcoming current barriers, paving the way for the development of robust, high-performance, and commercially viable gas sensors that align with global sustainability goals.

Purpose: Induction of ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, holds promise as a novel cancer therapy. Superparamagnetic iron oxide nanoparticles (SPIONs) have been proven able to induce ferroptosis in tumour cells, while their effects on non-cancerous cells remain unclear. In this study, we investigated the ability of silica-coated SPIONs to induce ferroptosis in human umbilical vein endothelial cells (HUVEC) and explored the potential protective effects of oleic acid (OA). Additionally, we evaluated the applicability of scanning electron microscopy (SEM) in distinguishing between ferroptotic and apoptotic cell death.

Results: We confirmed that silica-coated SPIONs, (used at concentrations of 25 and 50 µg/mL) increased lipid peroxidation and ROS formation in a dose-dependent manner up to 4.9- and 4-fold compared to controls, ultimately promoting ferroptosis without evidence of apoptosis, as indicated by the absence of phosphatidylserine-positive, propidium iodide-negative cells in flow cytometry experiments. Consistent with these results, the ferroptosis inhibitors α-tocopherol and ferrostatin-1 attenuated SPION-induced cytotoxicity, supporting ferroptosis as the primary mechanism of cell death. OA also protected cells from SPION-induced cytotoxicity by reducing lipid peroxidation, ROS formation, and cell death (from 58% to 26%), while increasing glutathione peroxidase expression. Unfortunately, due to the similar surface morphology of ferroptotic and apoptotic cells, SEM is not a reliable method for distinguishing between these two forms of cell death.

Conclusion: This study provides important insights into the mechanisms of toxicity of silica-coated SPIONs in endothelial cells and highlights the potential role of OA as a modulator of SPION-induced side effects.

Orthopedic regenerative medicine faces significant challenges in treating critical-sized bone defects, infections, and achieving spatiotemporal therapeutic control. Traditional hydrogels, while providing a biocompatible three-dimensional (3D) environment, often lack the dynamic responsiveness and mechanical strength required for effective bone repair. The integration of magnetic nanoparticles (MNPs), particularly iron oxides (Fe₃O₄, γ-Fe₂O₃), into hydrogel matrices has emerged as a transformative strategy to overcome these limitations. These magnetic nanocomposite hydrogels (MNHs) leverage the unique superparamagnetic properties of MNPs to enable remote and non-invasive control over their structure and function via external magnetic fields. This review comprehensively explores the design principles, synthesis methodologies, and multifaceted applications of MNHs in orthopedics. Key advancements discussed include their role in enhancing targeted drug delivery (eg, on-demand antibiotic or growth factor release), facilitating cell-based therapies through magnetic retention and mechanostimulation of mesenchymal stem cells (MSCs), and serving as dynamic scaffolds for bone tissue engineering with improved osteogenic commitment. Furthermore, MNHs exhibit great promise in anti-infective therapies by leveraging magnetic hyperthermia to eradicate biofilms and in diagnostic monitoring as contrast agents for MR. Despite their immense potential, clinical translation is contingent upon addressing critical challenges such as long-term biocompatibility of MNPs, scalability of fabrication, and achieving precise in vivo control of magnetic fields. Future perspectives highlight the convergence of MNHs with 4D bioprinting and artificial intelligence (AI) for designing patient-specific, intelligent systems. This review concludes that MNHs represent a paradigm shift towards personalized and adaptive regenerative solutions, poised to redefine treatment strategies in orthopedics and beyond.

Objective: Andrographolide (AG) demonstrated promising anticancer efficacy against the initiation and progression of breast cancer by triggering the mitochondria-mediated intrinsic apoptotic pathway. However, its clinical translation is still hindered by drawbacks such as poor bioavailability and off-target effects; therefore, an optimized drug-delivery system that minimizes these effects is urgently needed. To address these issues, we successfully developed a mitochondria-targeting nanocarrier (TPP-PEG-PCL) with high drug-loading capacity and excellent biocompatibility.

Methods: The mitochondria-targeting copolymer (TPP-PEG-PCL) was synthesized chemically and used to prepare AG-loaded polymeric micelles (TPP-PEG-PCL@AG) by solvent-evaporation method. In vitro, the blank micelles were first evaluated for biocompatibility with mouse breast-cancer cells (4T1) and endothelial cells (EC). Subsequently, a panel of cellular assays was performed on 4T1 cells to compare the antitumor activity of free AG, PEG-PCL@AG, and TPP-PEG-PCL@AG, confirming the enhanced cancer-cell killing achieved through mitochondria-targeted delivery of AG.

Results: The results showed that TPP-PEG-PCL micelles were readily taken up by 4T1 cells and selectively accumulated in mitochondria with a Pearson's correlation (Rr) 0.47 compared to 0.25 in PEG-PCL micelles group, leading to a pronounced inhibition of proliferation and migration. By elevating intracellular ROS, decreasing mitochondrial membrane potential, and activating the caspase cascade, the micelles induced apoptosis and thereby achieved mitochondria-targeted potentiation of TPP-PEG-PCL@AG. However, this study is limited to in vitro validation using the 4T1 murine model, and further in vivo investigations are warranted to assess translational efficacy and potential systemic toxicity..

Conclusion: PCL-PEG nanoparticles decorated with TPP combine pronounced mitochondria-targeting specificity, high drug-loading capacity, excellent biocompatibility and readily tunable architecture, making them an ideal platform for constructing a precise mitochondrial-intervention system for AG. This strategy is particularly attractive for tumor-targeted delivery of AG and opens a new avenue for its clinical translation.