International Journal of Nanomedicine最新文献

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.

Background: Graphene oxide (GO) has high drug-loading capacity and good photothermal property. However, the limited stability and poor biocompatibility of GO hindered its application as drug delivery carrier for future nanomedicine.

Methods: In this study, a new strategy of using chemical conjugation on GO with polypeptide was adopted. A novel Biotin grafted polysarcosine polymers (B-PSar) modified graphene oxide derivative (B-PSar-GO) was successfully synthesized and utilized as a carrier to develop a new drug delivery system for targeted chemo-photothermal cancer therapy. In vitro and in vivo experiments evaluated the system's biosafety and antitumor efficacy.

Results: With the B-PSar protection, the B-PSar-GO showed excellent biological safety with the average size of 268.2±8.4 nm. Stability experiments displayed B-PSar-GO was extremely stable. The anti-cancer drug doxorubicin (DOX) was loaded on B-PSar-GO through π-π interactions and hydrophobic interactions, B-PSar-GO@DOX achieved a maximum loading capacity of 25.5%. In addition, B-PSar-GO@DOX exhibited NIR/pH dual-responsive DOX release characteristics, ensuring sustained drug release to tumor tissues triggered by NIR laser irradiation and acidic tumor microenvironment. Based on the excellent photothermal conversion efficiency of GO, B-PSar-GO@DOX showed excellent chemo-photothermal synergistic tumor inhibition both in vitro and in vivo under NIR irradiation.

Conclusion: The novel nano-drug delivery system B-PSar-GO@DOX developed in this paper offers a promising platform for chemo-photothermal synergistic cancer treatment.

Chronic wounds, such as diabetic foot ulcers, venous leg ulcers, and pressure sores, pose a significant clinical challenge due to ongoing inflammation, biofilm development, and impaired tissue regeneration. Standard wound care methods often fail to address these complex barriers, highlighting the need for innovative solutions. Nanorobotics has emerged as a groundbreaking platform, enabling programmable, multifunctional systems capable of active navigation, biofilm penetration, modulation of the microenvironment, and targeted therapeutic delivery. This review systematically covers the design principles and functional components of micro-/nanorobots, including propulsion techniques, sensing and actuation mechanisms, and biomimetic surface modifications. We also examine their therapeutic potential in wound healing, focusing on drug delivery optimization, biofilm disruption, reduction of oxidative stress, immune regulation, and tissue regeneration support. The integration of nanorobotics with intelligent wound care systems offers real-time monitoring and closed-loop interventions, initiating a new era of "smart wound management." Finally, we address translational challenges such as biosafety, large-scale manufacturing, and regulatory pathways, and provide perspectives on future advancements toward clinically practical, intelligent nanorobotic wound therapies.

Bladder cancer (BC) is a prevalent urinary malignancy characterized by high recurrence rates and suboptimal long-term outcomes from traditional treatments such as surgery, chemotherapy, and radiotherapy. T-cell-based immunotherapy has emerged as a promising approach, harnessing T cells' capacity to target and destroy tumor cells, yet it faces challenges from the immunosuppressive tumor microenvironment (TME), immune evasion, and T-cell exhaustion. Nanomaterials offer innovative solutions by enabling targeted delivery of antigens, checkpoint inhibitors, and immunomodulators; remodeling the TME through metabolic interventions (eg, hypoxia alleviation and adenosine reduction); and enhancing T-cell infiltration and persistence with stimulus-responsive systems like pH-sensitive nanoparticles and biomimetic vesicles. This review systematically examines nanomaterial integration to amplify T-cell-mediated immunity in BC, covering T-cell origins, differentiation (eg, CD8+ cytotoxic and CD4+ helper subsets), roles in the TME, and exhaustion mechanisms driven by factors like PD-1 and TOX. We discuss key strategies including direct immune enhancement via immunogenic cell death induction, metabolic reprogramming to optimize T-cell function, and sustained activation for improved persistence. In conclusion, these nanomaterial-enhanced therapies address critical barriers, promoting precise and synergistic immune responses. Future prospects highlight AI-driven designs, personalized medicine, and clinical translation to tackle heterogeneity, biosafety, and resistance for durable BC remission.

With the rising incidence and mortality rates of melanoma, the limitations of traditional treatment methods have become increasingly evident. These approaches often lack precision, cause systemic toxicity, or fail to prevent recurrence, falling short of current treatment needs such as efficacy, safety, and long-term tumor control. Melanoma progression involves complex biological features such as uncontrolled proliferation, immune evasion, and metastasis, which are crucial for understanding clinical behavior and guiding treatment design. Hydrogels have recently emerged as a promising platform in the field of cancer therapy due to their tunable physicochemical properties, biocompatibility, and capacity for localized, controlled drug delivery. To provide a comprehensive and methodologically sound overview, we systematically searched the PubMed database using the keywords "hydrogel" and "melanoma" for studies published up to December 2024. Studies were screened based on relevance, originality, and experimental support. This review focuses on hydrogel-based strategies for melanoma treatment, highlighting: (1) recent advances in hydrogel design and functionality; (2) their integration with therapeutic approaches such as immunotherapy, chemotherapy, and photothermal therapy; and (3) their potential in postoperative wound management. In addition, we discuss the role of material selection in hydrogel performance and explore how the combination of distinct therapeutic approaches within hydrogel systems can synergistically improve treatment outcomes. Finally, we address the current challenges facing clinical translation, including safety, efficacy, and regulatory hurdles, while outlining potential pathways to overcome these barriers. This review aims to support future research and clinical innovation by providing a structured, up-to-date overview of hydrogel applications in melanoma therapy.