International Journal of Nanomedicine最新文献

Aging is a complex biological process characterized by progressive loss of physiological integrityand represents the primary risk factor for numerous chronic disorders, including neurodegenerative diseases, diabetes mellitus, cardiovascular disease, and stroke. Increasing evidence indicates that chronic low-grade inflammation ("inflammaging"), genomic instability, mitochondrial dysfunction, deregulated nutrient sensing, cellular senescence, and impaired intercellular communication collectively drive aging and age-related pathologies. Extracellular vesicles (EVs), a heterogeneous population of lipid bilayer-enclosed nanoparticles released by nearly all cell types, have emerged as critical regulators of these processes by mediating intercellular transfer of proteins, lipids, metabolites, and nucleic acids. In this review, we systematically synthesize current advances in EV biology within the context of aging and major age-related diseases, emphasizing their double-edged roles in disease pathogenesis and therapy. We discuss how senescent or diseased cell-derived EVs propagate inflammation, oxidative stress, genomic damage, mitochondrial dysfunction, and maladaptive immune responses, thereby accelerating tissue degeneration. Conversely, EVs derived from stem cells or young, healthy tissues exert therapeutic and rejuvenating effects by restoring redox balance, modulating immune polarization, enhancing mitochondrial function, regulating nutrient-sensing pathways, and promoting tissue repair and regeneration. Finally, we highlight the therapeutic potential of native and engineered EVs as diagnostic biomarkers and treatment modalities for aging and age-related diseases, while discussing key limitations, including rapid systemic clearance and targeting efficiency. Collectively, this review provides a comprehensive and therapy-oriented framework for understanding EVs as both drivers of aging-associated pathology and promising tools for anti-aging and regenerative medicine.

Hepatocellular carcinoma (HCC) remains one of the most aggressive malignancies, with poor prognosis and limited treatment options, particularly due to the immunosuppressive tumor immune microenvironment (TIME). Hydrogels have emerged as a promising biomaterial platform for local and controlled delivery of immunomodulatory agents, offering a novel strategy to remodel the TIME and enhance the efficacy of existing therapies. This review explores hydrogel-based strategies for immunomodulation in HCC, focusing on their potential to localize immune regulation, improve immune cell infiltration, and overcome immune evasion. Hydrogels can be engineered to encapsulate a range of therapeutic agents, including immune checkpoint inhibitors, cytokines, tumor antigens, and adjuvants, allowing for sustained release and targeted action within the tumor. The integration of hydrogels with therapies such as ablation, CAR-T cell therapy, and tumor vaccines has demonstrated synergistic effects, significantly enhancing antitumor immunity and reducing tumor recurrence. However, challenges remain in optimizing hydrogel composition, biocompatibility, degradation rates, and the efficiency of agent delivery. Personalized hydrogel-based therapies, tailored to individual patient's TIME, hold great potential for precision immunotherapy in HCC. This review highlights the current advances, challenges, and future directions for hydrogel-based immunomodulation strategies in HCC treatment, underscoring their transformative potential in cancer therapy.

Extracellular vesicles (EVs) derived from macrophages have emerged as critical regulators of tumor progression by functioning as polarization-dependent carriers of bioactive molecular information. Rather than acting as passive byproducts, macrophage-derived EVs reflect the activation state of their parent cells and actively reprogram tumor behavior and the tumor microenvironment. In this review, we propose a conceptual framework in which macrophage-derived EVs serve as information hubs that link macrophage polarization, selective cargo loading, and coordinated modulation of tumor and immune cell phenotypes. EVs released from classically activated (M1) macrophages predominantly convey tumor-suppressive signals, including specific noncoding RNAs and immunomodulatory proteins, thereby inhibiting tumor proliferation, invasion, immune evasion, and therapeutic resistance while reinforcing anti-tumor immunity. In contrast, EVs derived from alternatively activated (M2) macrophages deliver a coherent pro-tumor program that integrates epithelial-mesenchymal transition, metabolic reprogramming, stemness maintenance, ferroptosis resistance, immune suppression, and therapy tolerance across multiple cancer types. We systematically summarize the emerging mechanisms governing polarization-dependent cargo selection, including RNA-binding protein-mediated sorting, metabolic and signaling pathway control, and EV biogenesis regulation. In addition, this review highlights the translational implications of macrophage-derived EVs as engineering-ready platforms. We discuss strategies to enhance the therapeutic utility of M1 EVs through cargo engineering and surface functionalization, as well as approaches to disrupt, reprogram, or selectively block M2 EV-mediated oncogenic information flow. Collectively, this work advances a unifying molecular and translational perspective, positioning macrophage-derived EVs as actionable targets and tools for precision modulation of the tumor microenvironment in cancer diagnosis and therapy.

This review explores nanocapsules as a versatile platform to overcome the limitations of drug resistance inherent in conventional cancer therapy and immunotherapy. These nanosystems are capable of enhancing drug delivery, facilitating immune activation and modulating the tumor microenvironment. The review systematically classifies nanocapsules into distinct categories, including bacterial carriers, protein frameworks, lipids, metals, inorganic non-metals and polymers. Key findings demonstrate that nanocapsules possess the capacities for targeted delivery, stimuli-responsive release and synergistic combination with chemotherapy, radiotherapy, as well as photodynamic/photothermal therapy. However, several hurdles remain for their clinical translation, namely insufficient clinical trials and challenges in production scalability. In addition, the review discusses the impacts of different physical properties of nanocapsules and the underlying mechanisms of drug resistance. By uniquely integrating the classification of nanocapsules with corresponding therapeutic strategies, this review provides valuable insights for improving the efficacy of tumor immunotherapy.

Background: The theranostic potential of glycine-derived carbon dots (Gly/CDs) against arsenic-induced hepatotoxicity remains largely unexplored. This study aimed to synthesize Gly/CDs via a green, microwave-assisted method and to systematically evaluate their hepatoprotective efficacy and underlying mechanisms in a sodium arsenite (NaAsO₂)-induced hepatic injury model.

Methods: Gly/CDs were synthesized using citric acid, urea, and glycine as precursors. Their physicochemical properties were characterized using transmission electron microscopy (TEM), fluorescence spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and X-ray photoelectron spectroscopy (XPS). Following in vivo biocompatibility assessment, a murine model of NaAsO₂-induced hepatotoxicity was established to evaluate therapeutic efficacy. Comprehensive biochemical assays, histopathological examinations, and transcriptomic analyses were conducted to assess oxidative stress, inflammatory responses, DNA damage, apoptosis, fibrosis, and the involved molecular pathways.

Results: Gly/CDs exhibited excellent biocompatibility and demonstrated significant hepatoprotective effects, including restoration of redox homeostasis, suppression of pro-inflammatory cytokines, and attenuation of hepatocellular DNA damage, apoptosis, and fibrotic remodeling. Transcriptomic profiling suggested the involvement of the PI3K/AKT signaling pathway as a key molecular axis associated with the observed therapeutic effects. Overall, Gly/CDs preserved hepatic structure and function under chronic arsenic exposure.

Conclusion: This study provides the first comprehensive evidence that Gly/CDs function as biologically active nano-antioxidants capable of mitigating arsenic-induced hepatotoxicity through redox modulation and modulation of PI3K/AKT signaling activity. Given their low toxicity, ease of synthesis, and multifunctional properties, Gly/CDs represent a promising nanotherapeutic platform for applications in redox biology, toxicology, and environmental health.

Introduction: The management of chronic infected wounds imposes a substantial economic burden on patients and significantly impairs their quality of life due to persistent wound infections and delayed healing. To address this issue, we developed a multifunctional dressing with sustained hydrogen sulfide (H₂S) release to accelerate wound healing.

Methods: Sodium hydrosulfide-loaded cerium oxide (NaSH@CeO₂) was synthesized via rotary evaporation and subsequently incorporated into a hydrogel dressing crosslinked with chitosan (CS) and hyaluronic acid (HA), yielding NaSH@CeO₂/CS-HA. The composite was characterized, and H₂S release was quantified using the methylene blue method. The biological functions of NaSH@CeO₂/CS-HA were evaluated through CCK-8 assay, Calcein-PI staining, DCFH-DA detection, scratch assay, tube formation assay, and antibacterial tests. A methicillin-resistant Staphylococcus aureus (MRSA)-infected wound model was established in rats to assess therapeutic efficacy based on wound healing rate, hematoxylin-eosin (H&E) staining, Masson's trichrome staining, and immunofluorescence staining.

Results: NaSH@CeO₂/CS-HA demonstrated sustained H₂S release without cytotoxicity while effectively inhibiting Escherichia coli and MRSA. Furthermore, it reduced intracellular reactive oxygen species levels, maintained cell viability under H₂O₂-induced oxidative stress, promoted mouse fibroblast cells (L929 cells) migration, and enhanced tube formation in human umbilical vein endothelial cells (HUVECs). In the MRSA-infected rat wound model, the NaSH@CeO₂/CS-HA group achieved a 98.1% wound closure rate by day 14. H&E and Masson's staining revealed enhanced tissue healing, while immunofluorescence (CD31, Caspase-3) confirmed increased angiogenesis and reduced apoptosis at the wound site.

Conclusion: The developed gel dressing (NaSH@CeO₂/CS-HA) intelligently regulates H₂S release, combining antioxidant, antibacterial, and wound-healing functions into one, providing a comprehensive treatment solution for chronic infectious wounds with significant clinical application potential.

Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Research indicates that inflammatory responses and oxidative stress mediated by reactive oxygen species (ROS) are hallmark pathological mechanisms of CVD. Traditional anti-inflammatory drugs, though widely used, have limitations such as lack of targeting, low systemic delivery efficiency, and significant side effects. Nanozymes are a class of nanomaterials with enzyme-like activity, and their breakthrough applications offer new directions for the prevention and treatment of CVD. In the treatment of cardiovascular diseases, nanozymes demonstrate unique advantages: they can achieve local targeted delivery and ROS scavenging, and can also regulate the inflammatory microenvironment through multi-mechanism interventions. However, despite their promising applications, nanozymes still face challenges such as optimizing catalytic selectivity, improving biological targeting efficiency, and verifying long-term safety. This article will review the mechanisms of action of nanozymes in inflammation regulation and summarize their applications in cardiovascular diseases.

Purpose: Breast cancer remains the leading cause of cancer-related death in women, largely due to therapy resistance driven by both tumor-intrinsic and tumor microenvironment (TME)-mediated mechanisms. Toll-like receptor 2 (TLR2), which is overexpressed in breast tumors, promotes cancer progression and chemoresistance through both cancer-cell intrinsic and immune-mediated signaling, making it a promising therapeutic target.

Methods: We developed a targeted therapy combining two types of nanoparticles (NPs) for targeted drug delivery, hybrid poly (lactic-co-glycolic acid) (PLGA)- lipid NPs loaded with the TLR2 inhibitor CU-CPT22 (PLGA-CU) and liposomes encapsulating doxorubicin (LIPO-DOXO). Both NP types were functionalized with cyclic RGD peptides to target α_vβ₃ integrins. Their effects were evaluated in vitro on triple-negative and HER2-positive breast cancer cells and in vivo in 4T1 triple negative breast cancer tumor-bearing mice.

Results: PLGA-CU effectively inhibited TLR2 signaling. Both PLGA-CU and LIPO-DOXO reduced cell viability and induced apoptosis, with stronger effects observed when used in combination. In vivo imaging confirmed the accumulation of NPs in tumors. While monotherapies reduced tumor growth, the combined treatment targeted both cancer cells and TME, leading to reduced angiogenesis and immunosuppression, as well as enhanced anti-tumor activity.

Conclusion: NP-mediated delivery of a TLR2 inhibitor and doxorubicin produces synergistic anti-cancer effects in breast cancer models. This approach may help overcome chemoresistance and improve therapeutic outcomes, offering a promising strategy for the treatment of advanced breast cancer.

Cell membrane-coated nanoparticles (CMNPs) have emerged as a promising platform for targeted drug delivery and therapeutic applications due to their unique properties, such as improved biocompatibility, prolonged circulation time, and ability to mimic natural cell functions. The preparation of CMNPs involves three critical stages: extraction of the cell membrane, preparation of the nanoparticle core, and membrane coating. The cell membrane is isolated through various methods, including hypotonic lysis, freeze-thaw cycles, and centrifugation, with careful attention paid to preserving its integrity and functionality. Nanoparticle cores, which can be organic (eg, PLGA, liposomes) or inorganic (eg, metal-based cores), offer distinct advantages in terms of drug loading capacity, stability, and therapeutic potential. The fusion of the core and the membrane is typically achieved through techniques such as membrane extrusion, sonication, and electroporation. These methods enable the efficient formation of core-shell nanostructures, which can be utilized for a range of biomedical applications, particularly in drug delivery, cancer therapy, and tissue regeneration. This review discusses the key aspects of CMNP preparation, including membrane extraction and purification techniques, core selection, and fusion methods, as well as the current trends and future directions in the development of CMNPs for therapeutic purposes.

Purpose: Pulmonary fibrosis (PF) is a progressive interstitial lung disease characterized by high morbidity and limited treatment options. Current antifibrotic agents, such as pirfenidone and nintedanib (NIN), are restricted by systemic toxicity and insufficient pulmonary targeting. This study aimed to develop an inhalable human serum albumin (HSA)-based nanoparticle system co-delivering NIN and dihydroartemisinin (DHA), termed DHA/NIN@HSA, to achieve efficient lung-targeted combinational therapy against PF.

Methods: DHA/NIN@HSA nanoparticles were prepared via a self-assembly strategy and characterized for morphology, particle size, and drug-loading efficiency. Pulmonary deposition and retention profiles after airway inhalation were evaluated using in vivo fluorescence imaging. The antifibrotic efficacy and safety of DHA/NIN@HSA were further assessed in a bleomycin-induced PF mouse model.

Results: DHA/NIN@HSA nanoparticles exhibited uniform particle size (125 ± 5 nm) and excellent pulmonary deposition, ensuring prolonged lung retention and reduced systemic exposure. Airway administration of DHA/NIN@HSA every 48 h significantly mitigated fibrosis progression, improved survival, and restored alveolar architecture. Mechanistically, NIN inhibited fibroblast proliferation and myofibroblast differentiation, while DHA suppressed transforming growth factor-β1 (TGF-β1)/Smad2/3 signaling and inflammatory cytokines expression. Notably, DHA showed antifibrotic efficacy comparable to NIN with superior anti-inflammatory activity, highlighting its therapeutic potential in PF.

Conclusion: Airway co-delivery of DHA/NIN@HSA achieved maximal antifibrotic efficacy, precise lung targeting, and favorable safety, providing a translatable nanotherapeutic platform for combinational therapy of PF.