International Journal of Nanomedicine最新文献

{"title":"A Self-Regenerating Mixed-Valence FeO_x-TiO₂ Nanoplatform for Mitochondrion-Targeted Triple-Modal Cancer Therapy.","authors":"Yongzhi Xia, Mengqin Wang, Yanyan Zhou, Ruiqi Wei, Yijie Wang, Lijuan Hua, Qiang Fang, Yan Chen","doi":"10.2147/IJN.S629321","DOIUrl":"https://doi.org/10.2147/IJN.S629321","url":null,"abstract":"<p><strong>Purpose: </strong>Reactive oxygen species (ROS) cancer therapy is limited by short ROS lifetime, restricted diffusion, and lack of subcellular targeting. Current approaches physically mix independent components, causing complexity and decoupled actions. To overcome these barriers, we developed a mitochondrion-targeted nanoplatform (FTDT) built on a FeOₓ-TiO₂ composite core with intrinsic mixed-valence Fe²⁺/Fe³⁺ pairs. The FT core acts as photosensitizer, while FeOₓ provides catalase- and peroxidase-like activities, integrating self-oxygenation, antioxidant depletion, self-amplifying redox cycling, photosensitization, photothermal conversion, and organelle anchoring into a single entity.</p><p><strong>Methods: </strong>FTDT was synthesized via a hydrothermal method, PDA coating, and TPP conjugation. Mixed-valence state was confirmed by XPS. Catalase- and peroxidase-like activities were evaluated by O₂ and ∙OH detection. UV-Vis-NIR spectroscopy characterized optical absorption. Photothermal conversion was measured under 808 nm laser. ¹O₂ generation was detected using DPBF. Intracellular hypoxia, ROS, mitochondrial targeting, membrane potential, and lysosomal integrity were assessed by fluorescence microscopy. Cytotoxicity and in vivo efficacy were evaluated in A549 cells and xenograft mice.</p><p><strong>Results: </strong>FTDT showed a self-amplifying cycle: Fe²⁺ drives ∙OH generation, Fe³⁺ consumes GSH and regenerates Fe²⁺; Fe³⁺ from Fenton reaction replenishes the Fe³⁺ pool. The core converted H₂O₂ to O₂. FT core with PDA-enabled NIR absorption allowed ¹O₂ generation and photothermal conversion. TPP enabled mitochondrial localization, inducing dysfunction, lipid peroxidation, and lysosomal disruption, leading to cell death. In vitro and in vivo studies confirmed antitumor efficacy with good biocompatibility.</p><p><strong>Conclusion: </strong>By unifying self-oxygenation, antioxidant depletion, self-amplifying redox cycling, photosensitization, photothermal conversion, and organelle anchoring, FTDT offers a clinically translatable strategy to overcome key barriers in ROS-based cancer therapy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"629321"},"PeriodicalIF":8.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanoparticle-Mediated Brain-Targeted Drug Delivery for Methamphetamine Use Disorder: Advances, Challenges and Translational Perspectives.","authors":"Xinjie Zhang, Ruike Xu, Min Wang, Yan Du, Miao Zhang, Lihua Li, Genmeng Yang, Shijun Hong","doi":"10.2147/IJN.S625117","DOIUrl":"https://doi.org/10.2147/IJN.S625117","url":null,"abstract":"<p><p>Methamphetamine use disorder (MUD) poses a significant global health challenge, lacking FDA-approved pharmacotherapies. Despite extensive exploration of therapeutic targets and interventions, effective treatment remains scarce due to challenges in delivering therapeutic agents to relevant brain regions at effective concentrations. Nanoparticle-mediated delivery offers a promising approach for transporting various therapeutic cargos to the central nervous system, including small molecules, nucleic acids, peptides, proteins, and gene-editing systems. However, the application of nanomedicine strategies in addressing the unique pathophysiological characteristics of MUD has not been systematically assessed. This review presents a problem-focused analysis of how lipid-based, polymeric, inorganic, biological, and hybrid nanocarriers tackle successive delivery obstacles such as systemic stability, blood-brain barrier (BBB) penetration, brain region-specific distribution, and controlled release of intracellular cargo. We compare preclinical nanotherapeutic approaches encompassing small-molecule neuroprotective agents, anti-METH vaccines, gene-silencing RNAs, neurotrophic proteins, and emerging gene-editing methods, outlining their respective benefits, limitations, and design considerations. Additionally, we explore key factors influencing nanomedicine performance in MUD, including protein corona formation, the impact of METH-related BBB dysfunction and neuroinflammation on nanoparticle distribution, and the disparity between acute animal models and chronic human MUD with relapse tendencies. In conclusion, we present a systematic framework for aligning nanocarrier characteristics with distinct delivery obstacles and therapeutic needs. We also emphasize forthcoming avenues such as disease-triggered nanocarriers, targeted delivery to specific regions, combined nanomedical approaches, theranostic strategies, and standardized assessments of biodistribution, effectiveness, safety, and translational potential.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"625117"},"PeriodicalIF":8.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PVP-Stabilized Ag@SiO₂ Nanocarriers for Usnic Acid: Physicochemical Characterization and Exploratory in vitro Anticancer, Antimicrobial, and Immunomodulatory Activity.","authors":"Agnieszka Pyrczak-Felczykowska, Agata Kowalska, Elżbieta Adamska, Aleksandra Bogucka, Katarzyna Zima, Dariusz Nowicki, Klaudia Żuczek, Anna Wcisło, Beata Grobelna, Krzysztof Urbanowicz, Magdalena Zabielska-Kaczorowska, Anna Herman-Antosiewicz","doi":"10.2147/IJN.S629377","DOIUrl":"https://doi.org/10.2147/IJN.S629377","url":null,"abstract":"<p><strong>Background: </strong>Usnic acid (UA) is a lichen-derived metabolite with recognized anticancer, anti-inflammatory, and antibacterial properties; however, its clinical application is limited by poor aqueous solubility and dose-dependent toxicity. This study aimed to develop a multifunctional nanosystem to improve UA aqueous dispersibility and efficacy against breast cancer cells in vitro.</p><p><strong>Methods: </strong>A nanosystem consisting of a silver core-silica shell coated with polyvinylpyrrolidone (PVP) and conjugated UA (Ag@SiO₂/PVP/UA) was synthesized and characterized regarding morphology, physicochemical properties, colloidal stability, drug loading, and release behavior. Antiproliferative activity was evaluated using breast cancer cells (MCF-7 and MDA-MB-231). Cytotoxicity was assessed using the MTT viability assay, reactive oxygen species (ROS) production by flow cytometry, and metabolic alterations through LC-MS/MS-based metabolomic analysis. Antimicrobial activity against Gram-positive and Gram-negative bacteria was expressed by minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Immunomodulatory properties were assessed in human peripheral blood mononuclear cells (PBMCs) using ELISA, while fibroblast migration was analyzed using an in vitro wound healing assay.</p><p><strong>Results: </strong>The developed nanostructures exhibited a stable core-shell architecture, uniform particle size (~200 nm), and enhanced hydrophilicity, resulting in improved aqueous dispersibility and sustained UA release. Nanoencapsulation significantly enhanced UA's anticancer activity against breast cancer cells in vitro while maintaining lower toxicity toward normal cells. Mechanistically, Ag@SiO₂/PVP/UA induced ROS-mediated oxidative stress and metabolic reprogramming associated with altered purine metabolism, lipid biosynthesis, redox balance, and activation of glycolytic pathways. The nanosystem also demonstrated broad-spectrum antimicrobial activity, including improved efficacy against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and selected Gram-negative bacteria, while exerting immunomodulatory effects by reducing pro-inflammatory cytokine secretion and enhancing IL-10 production without affecting fibroblast migration.</p><p><strong>Conclusion: </strong>Ag@SiO₂/PVP/UA represents a promising multifunctional therapeutic platform combining enhanced anticancer efficacy with antimicrobial and anti-inflammatory properties, potentially improving the therapeutic applicability of UA.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"629377"},"PeriodicalIF":8.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13679582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes Derived from Sea Cucumbers in Indonesian Marine for Anti-Aging and Skin Regeneration.","authors":"Muhaimin Muhaimin, Anis Yohana Chaerunisaa, Miski Aghnia Khairinisa, Eko Sri Wahyuningsih, Barmi Hartesi, Faizal Hermanto, Ruslin Ruslin, Suryani Suryani","doi":"10.2147/IJN.S648038","DOIUrl":"10.2147/IJN.S648038","url":null,"abstract":"<p><p>Indonesia's marine ecosystem is rich in biodiversity, including sea cucumbers that contain a range of potentially valuable bioactive compounds. Among these, exosomes-nanosized extracellular vesicles (EVs) that transport biological molecules between cells-are attracting interest as possible tools for anti-aging and skin regeneration. This review summarizes current knowledge about sea cucumber-derived exosomes and considers their potential applications in skincare and tissue repair. Sea cucumber exosomes may offer several advantages over the use of isolated compounds alone. Their vesicle structure can help protect and transport bioactive molecules, potentially supporting their delivery to target cells. Reported or proposed activities include antioxidant and anti-inflammatory effects, which may help limit oxidative stress and inflammation associated with skin aging. Exosomes may also support collagen production and skin elasticity, while promoting wound healing and tissue recovery. By influencing skin-cell communication and immune responses, they can contribute to a more coordinated regenerative process. These properties make sea cucumber exosomes a promising subject for research into multifunctional skincare approaches. Their potential use also highlights the value of Indonesia's marine resources and may encourage the development of locally sourced, nature-based products. However, sustainability depends on responsible harvesting and processing, and further research is needed to establish exosome composition, production methods, safety, efficacy, and long-term effects. In particular, laboratory findings must be validated through well-designed clinical studies before therapeutic or cosmetic claims can be confirmed. Overall, sea cucumber-derived exosomes from Indonesian marine ecosystems represent a promising area of research for anti-aging and skin regeneration. Their potential combination of bioactive cargo, cellular delivery, and regenerative effects may inform future skincare products and therapies, provided that development is supported by rigorous evidence and environmentally responsible practices.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"648038"},"PeriodicalIF":8.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poloxamer-Based Th1-Biased NKT Cell Nano-Agonist for Tumor Immunotherapy.","authors":"Weiwei Ma, Xuejing Zhai, Mengxiang Wang, Xueying Guo, Jinying Liang, Yanyan Yin","doi":"10.2147/IJN.S638980","DOIUrl":"10.2147/IJN.S638980","url":null,"abstract":"<p><strong>Background: </strong>Natural killer T (NKT) cells bridge innate and adaptive immunity and are promising targets for tumor immunotherapy. However, its agonist α-GalCer induces NKT cells to secrete both Th1-type and Th2-type cytokines. Coupled with the challenges of in vivo delivery, these drawbacks collectively limit its clinical application.</p><p><strong>Methods: </strong>In this study, we constructed Th1-biased NKT cell nano-agonists (LGCP Ms) by using Th1-preferred glycolipids (Lys-α-GalCer) and Poloxamer through thin-film hydration combined with probe sonication to enhance NKT cell-mediated anti-tumor immunity.</p><p><strong>Results: </strong>LGCP Ms exhibited a uniform spherical morphology with a mean size of 109.1 ± 0.85 nm, a Zeta potential of -15.7 ± 1.2 mV. In vitro and in vivo results demonstrated that the nano-agonist efficiently activated NKT cells and significantly elevated Th1-type cytokine levels. In a murine Hepa1-6 cell tumor model, intraperitoneal injection of LGCP Ms significantly promoted Th1-type cytokine secretion, increased the proportions of NKT cells and CD8⁺ T cells in the spleen, and enhanced the infiltration of CD8⁺ T cells into tumor tissues. Finally, LGCP Ms showed considerably better anticancer activity compared to free α-GalCer both in vitro and in vivo.</p><p><strong>Conclusion: </strong>These findings demonstrated that the LGCP Ms nanodelivery system features facile preparation, high encapsulation efficiency, and favorable stability. LGCP Ms induced robust cytokine secretion and modulated NKT cell proportions, confirming effective NKT‑cell stimulation. This potent activation translates into substantial anti‑tumor immunity, positioning LGCP Ms as a promising strategy for cancer immunotherapy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"638980"},"PeriodicalIF":8.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Folic Acid-Conjugated Albumin-Stabilized Gold-Terbium Nanoparticles for SPCCT/MRI Imaging: An in vitro Cellular and Phantom Study.","authors":"Yusuf O Ibrahim, Nabil Maalej, Aamir Younis Raja, Ahsanulhaq Qurashi, Mohamed Rahmani, Osama Abdullah, Fazila Sirajudeen, Rasha Nasser, Charalampos Pitsalidis, Mira Mousa","doi":"10.2147/IJN.S584189","DOIUrl":"https://doi.org/10.2147/IJN.S584189","url":null,"abstract":"<p><strong>Introduction: </strong>Triple-negative breast cancer (TNBC) remains challenging to image because of its biological heterogeneity and the limitations of single-modality imaging. Multifunctional nanoparticles may provide complementary contrast for spectral photon-counting CT (SPCCT) and MRI, potentially improving multimodal tumor imaging.</p><p><strong>Methods: </strong>Folic acid-conjugated, albumin-stabilized gold-terbium nanoparticles (BSA@Au/Tb-FA) were synthesized and characterized using TEM, XRD, FTIR, XPS, and DLS. In vitro cellular uptake, cytotoxicity, and hemocompatibility were evaluated using MDA-MB-231 cells using confocal microscopy and flow cytometry. SPCCT and MRI performance were assessed in phantom models.</p><p><strong>Results: </strong>The BSA@Au/Tb-FA nanoparticles exhibited a spherical-like morphology, with a mean particle size of ~10.68 ± 1.69 nm (n = 55). Cell viability remained >80% up to 250 µg/mL, with an IC₅₀ of 352 µg/mL. The hemocompatibility was good, with hemolysis values below the ASTM safety threshold of 5% at 200 µg/mL. The materials demonstrated concentration-dependent cellular uptake at 25, 50, and 100 µg/mL, with BSA@Au/Tb-FA nanoparticles exhibiting higher uptake than the non-FA-conjugated nanoparticles, BSA@Au/Tb (p < 0.05). SPCCT showed an attenuation efficiency of 38.35 HU·mL·mg⁻¹ for BSA@Au/Tb-FA, attributable to the strong X-ray attenuation of Au and Tb components near their K-edge energies. Material decomposition showed strong agreement between measured and experimental concentrations <i>(R²</i> = 0.98). MRI phantom studies revealed relaxivity values of r₁ = 1.42 mM⁻¹s⁻¹ and r₂ = 13.82 mM⁻¹s⁻¹, indicating a dominant transverse relaxation effect and T₂-weighted contrast capability.</p><p><strong>Conclusion: </strong>BSA@Au/Tb-FA exhibited favorable in vitro hemocompatibility and biocompatibility, with enhanced cellular uptake in MDA-MB-231 and complementary enhanced SPCCT/MRI contrast under phantom conditions, supporting its potential as a bimodal imaging agent. However, because cellular evaluation was limited to MDA-MB-231 cells without a receptor-blocking study, the enhanced uptake should not be interpreted as confirmed folate-receptor-mediated targeting. Further preclinical and in vivo studies are required to establish targeting specificity, safety, and imaging performance.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"584189"},"PeriodicalIF":8.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breaking the Black Box: Revolutionizing Traditional Chinese Medicine with Formula-Derived Nanoparticles.","authors":"Mingrong Cheng, Peng Wen, Liqing Jiang, Hua Shen, Hua Wang","doi":"10.2147/IJN.S648153","DOIUrl":"10.2147/IJN.S648153","url":null,"abstract":"<p><p>Traditional Chinese medicine (TCM) formulas produce distinctive multi‑target synergistic therapeutic effects governed by the monarch, minister, assistant, and guide compatibility principle for diverse chronic and refractory disorders. Nevertheless, a four‑layer \"black‑box\" barrier-encompassing poorly characterized bioactive constituents, ambiguous inter‑component synergistic mechanisms, untraceable in vivo transport profiles, and low oral bioavailability-substantially hinders TCM modernization and global adoption. Most existing reviews focus on single‑component nanocarriers or plant‑derived extracellular‑vesicle‑like particles; few comprehensively investigate nanoparticles generated from complete multi‑herb TCM decoctions while integrating material characterization, mechanistic dissection, and clinical‑regulatory translational bottlenecks. This review addresses this literature gap by focusing on formula‑derived nanoparticles (FDNs), fabricated from intact TCM‑decoction extracts via natural self‑assembly or degradable exogenous carrier‑assisted assembly. FDNs largely retain native component ratios and synergistic bioactivities while enabling precise targeted delivery of herbal constituents. We summarize three mainstream FDN fabrication workflows and establish a comprehensive multidimensional characterization toolkit for assessing physicochemical properties, intermolecular interactions, structural stability, and biocompatibility. Enabled by three quantifiable technical approaches, FDNs can partially mitigate the TCM black‑box dilemma and exert multitarget, precision‑guided intervention against tumors, inflammatory bowel disease, neurodegenerative conditions, and metabolic disorders. Major translational obstacles include non‑standardized industrial scale‑up, insufficient biological barrier penetration, poorly defined molecular interaction mechanisms, absence of unified multicomponent quality benchmarks, incomplete global regulatory frameworks, high manufacturing costs, and risks of poor batch‑to‑batch reproducibility. Priority future directions cover intelligent biomimetic carriers, multiomics‑supported molecular simulation, and end‑to‑end standardized clinical translation, advancing empirical TCM‑formula therapeutics toward standardized, quantifiable high‑precision modern medicine. This review outlines actionable research gaps and a phased translational roadmap to guide investigations.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"648153"},"PeriodicalIF":8.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reconsidering the Classification of YTHDF2 in Glioblastoma [Letter].","authors":"Vilbert Sikorski, Joni Salo","doi":"10.2147/IJN.S658668","DOIUrl":"10.2147/IJN.S658668","url":null,"abstract":"","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"658668"},"PeriodicalIF":8.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nano-/Nanobiotechnology-Augmented Pyroptosis in the Treatment of Triple-Negative Breast Cancer: An Updated Review.","authors":"Jianquan Yang, Wen Guo, Xuezhou Pang, Zixin Li, Xun Wu, Yan Gui, Daiyuan Ma","doi":"10.2147/IJN.S624546","DOIUrl":"https://doi.org/10.2147/IJN.S624546","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC), a breast cancer subset defined by the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, faces persistent clinical challenges including narrow first-line treatment choices and inferior long-term survival rates. Immune checkpoint blockade has transformed clinical management across multiple malignancies, yet unselected TNBC patients exhibit only modest and heterogeneous clinical responses. This therapeutic resistance is primarily attributed to an immune-excluded tumor microenvironment (TME) with suppressed anti-tumor immunity, the hallmark of the so-called immunologically \"cold\" tumor phenotype. Pyroptosis, an inflammatory programmed cell death characterized by asdermin-mediated membrane pore formation and pro-inflammatory mediator secretion, triggers potent tumor immunogenic cell death and reverses the immunosuppressive TME state. Rationally designed nanoscale delivery vehicles enable tumor-localized delivery of pyroptosis agonists, minimizing off-target activation in normal tissues; this targeted induction boosts intratumoral cytotoxic CD8⁺ T cell infiltration, drives the immunophenotypic shift from \"cold\" to \"hot\" tumors in TNBC, and ultimately sensitizes tumors to immunotherapy. This review catalogs and contextualizes current preclinical progress on pyroptosis-triggering biomaterials for TNBC intervention, organized around three interconnected themes: design rationales for diverse nanoplatforms, molecular cascades of canonical and non-canonical pyroptosis signaling, and the immune-sensitizing roles of nanomediated pyroptosis in TNBC. Furthermore, this work highlights underaddressed translational barriers in the field: the mismatch between tumor tissue accumulation and intracellular pyroptosis activation efficiency, the lack of precise spatiotemporal control over pyroptotic magnitude, and the unmitigated risk of systemic inflammatory adverse events. Addressing these remaining knowledge gaps in the field, this review defines core priority research directions, namely subcellular-targeted delivery platforms, switchable pyroptosis modulation strategies, and combined therapeutic modalities that exert synergistic anti-tumor effects. Overall, this work establishes a structured, translational pathway for advancing pyroptosis-based nanotherapeutic strategies and improving clinical immunotherapy outcomes in patients with TNBC.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"624546"},"PeriodicalIF":8.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Graphene Oxide-Doped CuMOF Nanoplatform Enhances Chemodynamic Therapy and Suppresses CYP2J2-Mediated Linoleic Acid Metabolism in Castration-Resistant Prostate Cancer.","authors":"Guoqiang Qin, Xin Luo, Ge Zou, Qishan Mo, Weide Zhong","doi":"10.2147/IJN.S635163","DOIUrl":"10.2147/IJN.S635163","url":null,"abstract":"<p><strong>Purpose: </strong>Castration-resistant prostate cancer (CRPC) responds poorly to current therapies. A tumor microenvironment-responsive nanoplatform was developed to couple chemodynamic therapy with modulation of oncogenic lipid metabolism.</p><p><strong>Methods: </strong>A graphene oxide-doped copper-based metal-organic framework (GO-CuMOF) was prepared by ultrasonicating solvothermally synthesized CuMOF with graphene oxide, and was characterized physicochemically. Its generation of hydroxyl radicals (•OH) was confirmed by a methylene blue degradation assay. Antitumor activity was evaluated in DU145 and PC3 cells and in a PC3 xenograft model. Untargeted metabolomic and proteomic profiling was integrated with data from The Cancer Genome Atlas prostate adenocarcinoma cohort, and the candidate targets were validated by enzyme-linked immunosorbent assay (ELISA), reverse transcription quantitative PCR, and Western blotting.</p><p><strong>Results: </strong>In the presence of glutathione (GSH), GO-CuMOF released Cu⁺, depleting GSH and generating •OH. It raised intracellular reactive oxygen species (ROS), induced apoptosis, and suppressed CRPC cell proliferation and xenograft growth without reducing body weight or causing overt organ toxicity. Multi-omics profiling showed CYP2J2 downregulation, with accumulation of its substrate linoleate and reduction of 9(10)- and 12(13)-epoxyoctadecenoic acid (EpOME), the latter confirmed by ELISA. CYP2J2 was the most consistently associated candidate across proteomic and public-cohort evidence.</p><p><strong>Conclusion: </strong>GO-CuMOF exerts concurrent chemodynamic ROS generation and CYP2J2-associated changes in linoleic acid metabolism. The CYP2J2-EpOME axis represents a candidate metabolism-directed vulnerability for CRPC that warrants functional and clinical validation.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"635163"},"PeriodicalIF":8.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676870/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}