International Journal of Nanomedicine最新文献

{"title":"Release and Targeting Mechanism of Nanomedicine Delivery System in Inflammatory Bowel Disease.","authors":"Haichen Wang, Feifei Zhou, Mengdan Shen, Suya Zhou, Ronglin Ma, Qiang Yu","doi":"10.2147/IJN.S634650","DOIUrl":"10.2147/IJN.S634650","url":null,"abstract":"<p><p>Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), arises from multifactorial pathogenesis involving colonic barrier dysfunction, gut microbiota dysbiosis, and aberrant immune regulation. The complexity of these mechanisms poses substantial challenges to achieving curative outcomes, necessitating long-term maintenance therapies. Conventional therapeutic agents (5-aminosalicylic acids, glucocorticoids, immunosuppressants, and biologics) are constrained by inherent limitations including poor solubility, chemical instability, non-specific biodistribution, and off-target toxicity, which collectively compromise therapeutic efficacy and safety. To address these challenges, nanomaterial drug delivery systems (NDDS) have emerged as a transformative strategy to enhance drug solubility, achieve spatiotemporal control, and improve intestinal targeting while reducing systemic exposure. Building upon our prior review that established a taxonomy of NDDS, this review outlines the in vivo delivery mechanisms of nanomedicine delivery systems for IBD, with the organic integration of drug-loading strategies, drug administration routes, stimulus-responsive release, and targeting mechanisms as the core framework. By systematically integrating these multidimensional mechanisms throughout the entire drug administration lifecycle, this review constructs a theoretical framework that combines macroscopic vision with mechanistic depth, laying the foundation for the rational design of next-generation intelligent NDDS and providing systematic theoretical support for improving the treatment efficacy of IBD, minimizing systemic toxicity, and promoting the clinical translation of NDDS.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"634650"},"PeriodicalIF":8.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216197","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":"Evaluation of Modified Chitosan Nanomicelles with Carboplatin for Effective Treatment Against Ovarian Cancer Cell Types in Murine Model.","authors":"Agnieszka Piegat, Katarzyna Piotrowska, Danuta Kosik-Bogacka, Joanna Łapczuk-Romanska, Radosław Birger, Nina Komaniecka, Marek Drozdzik, Agnieszka Kempinska-Podhorodecka, Aneta Cymbaluk-Ploska","doi":"10.2147/IJN.S634858","DOIUrl":"10.2147/IJN.S634858","url":null,"abstract":"<p><strong>Introduction: </strong>The clinical efficacy of platinum-based chemotherapy in ovarian cancer is limited by insufficient drug retention within the peritoneal cavity and associated systemic toxicity. This study aimed to develop hydrophobically modified chitosan nanomicelles as a carrier system for localized carboplatin delivery.</p><p><strong>Methods: </strong>Hydrophobically modified chitosan nanomicelles were prepared using an oil-in-watr emulsification technique and characterized in terms of their physicochemical properties, stability, encapsulation efficiency, and drug release behaviour. In vitro studies were performed to assess biocompatibility and cellular internalization in MUC1-expressing SK-OV-3 ovarian cancer cells. The preliminary in vivo antitumour response to the carboplatin-loaded nanomicelles was further evaluated in a subcutaneous murine ovarian cancer xenograft model.</p><p><strong>Results: </strong>The obtained nanomicelles exhibited a mean hydrodynamic diameter of approximately 200 nm and an encapsulation efficiency of 44%. No quantifiable carboplatin release was detected within 24 h under the tested conditions; however, the absence of a quantifiable signal cannot distinguish limited early release from release below the quantifiable range of the analytical method. The nanomicelles demonstrated preliminary in vitro cytocompatibility in SK-OV-3 cells, with mean cell viability remaining above 70% under the tested conditions, and intracellular localization of the nanomicelles in MUC1-expressing SK-OV-3 cells was observed by confocal microscopy. At the end-point evaluation, tumours were significantly smaller in the nanomicelle-treated group than in the free-carboplatin group (p = 0.03), whereas exploratory longitudinal analysis of tumour-growth AUC showed no significant between-group difference (p = 0.67).</p><p><strong>Conclusion: </strong>Hydrophobically modified chitosan nanomicelles represent a feasible carrier platform for localized carboplatin delivery and warrant further investigation for potential intraperitoneal application. The observed drug encapsulation, lack of quantifiable carboplatin release during the 24-h study period, preliminary in vitro cytocompatibility in SK-OV-3 cells, cellular internalization, and preliminary antitumour response provide proof-of-concept support for continued evaluation of this carrier system.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"634858"},"PeriodicalIF":8.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13675965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216119","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 Multifunctional Metal-Based Nanomedicine for Copper Sequestration, in situ Toxification, and Immune Activation Against Metastatic Cancer.","authors":"Yingcai Meng, Weinan Wang, Wei Guo, Jiaxin Huang, Wenhu Zhou, Jianming Hu","doi":"10.2147/IJN.S580749","DOIUrl":"10.2147/IJN.S580749","url":null,"abstract":"<p><strong>Objective: </strong>Tumor metastasis remains the principal cause of cancer-related mortality. However, current therapies often fail to effectively control both primary and disseminated lesions. Copper ions (Cu²⁺) are increasingly being recognized as key regulators of tumor progression, metastasis, and immune evasion. Leveraging their tumor-promoting properties as therapeutic targets is a promising anticancer strategy.</p><p><strong>Methods: </strong>In this study, a multifunctional nanoplatform based on hyaluronic acid (HA)-stabilized and manganese-diethyldithiocarbamate (MnET) complex-loaded manganese dioxide (MnO₂) nanosheets, denoted as MMH (MnET@MnO₂-HA), was designed to deplete Cu²⁺ in the tumor microenvironment and simultaneously generate bioactive copper-diethyldithiocarbamate (CuET) in situ. MMH was systematically evaluated in terms of drug release, Cu²⁺ sequestration, in situ toxicity, and immune activation against primary and metastatic tumors, through both in vitro and in vivo experiments using animal models.</p><p><strong>Results: </strong>MMH exhibited CD44-targeted uptake, GSH- and pH-responsive drug release, and tumor-selective bioactivity. MMH efficiently scavenged Cu²⁺ within tumor cells, leading to the formation of CuET, which induced immunogenic cell death (ICD), marked by the release of damage associated molecular patterns (DAMPs). This process facilitated M1 macrophage repolarization, CD8⁺ T cell infiltration, and the activation of type I interferon signaling via Mn²⁺-mediated interferon regulatory factor 3 (IRF3) phosphorylation. Furthermore, MMH suppressed epithelial-mesenchymal transition (EMT) and vascular endothelial growth factor A (VEGF-A) expression, thereby impairing angiogenesis and metastatic spread. In murine 4T1 breast cancer models, MMH potently inhibited both primary and distant metastatic tumors without systemic toxicity.</p><p><strong>Conclusion: </strong>MMH would be a promising approach for treating aggressive and metastatic cancers through metal-based immunometabolic intervention.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"580749"},"PeriodicalIF":8.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216069","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":"Lipid Nanoparticle-Mediated Antifungal and Immunomodulatory Therapy for Neuromycoses.","authors":"Ruth Naomi, Hasnah Bahari, Yogeswaran Lokanathan, Hasniza Zaman Huri, Wei Lim Chong, Siti Aisyah Alias, Santhra Segaran Balan, Pamela David","doi":"10.2147/IJN.S634264","DOIUrl":"10.2147/IJN.S634264","url":null,"abstract":"<p><strong>Background: </strong>Neuromycoses, fungal infections affecting the central nervous system (CNS), cause approximately 112,000 deaths annually, representing 19% of AIDS-related deaths globally. Conventional antifungal drugs are limited by poor blood-brain barrier (BBB) penetration, systemic toxicity, and increasing drug resistance. Lipid nanoparticles (LNPs) have emerged as promising vehicles for enhancing antifungal efficacy while modulating immune responses. Thus, this comprehensive review synthesizes current knowledge on LNPs as vehicles for antifungal immune modulators, including their design principles, drug delivery mechanisms, physiological interactions, translational potential, and roadmap for next-generation precision medicine approaches to treating neuromycoses.</p><p><strong>Methods: </strong>A comprehensive narrative review of original studies on LNP-based approaches for neuromycoses was conducted. The literature was synthesized using a structured evidence table encompassing six studies published between 2019 and 2026, including one randomized clinical trial in adults, one case report, one in vitro study, two animal studies, and one study incorporating both in vitro and in vivo approaches. Original research studies were prioritized, while reviews, commentaries, and editorials were excluded.</p><p><strong>Findings: </strong>This review shows four principal findings: (1) LNP formulations achieved mean fungicidal activity of 0.402 log₁ ₀ CFU/mL/day, non-inferior to intravenous amphotericin B, with 18-week survival and reduced toxicity compared to intravenous formulations; (2) LNPs cross the BBB with limited or no systemic toxicity while enabling intracellular trafficking through optimization of lipid composition and surface chemistry; (3) RMT demonstrates high specificity affected by variability in receptor expression, while AMT and TMT operate through distinct mechanisms with their own potential off-target effects; and (4) encapsulation reduces nephrotoxicity and hepatotoxicity compared to free antifungal drugs, with amphotericin B-loaded NLC showing reduced nephrotoxicity in vitro compared to conventional formulations.</p><p><strong>Conclusion: </strong>These findings highlight the potential of LNP-based antifungal delivery and the need for further clinical validation before broader clinical translation.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"634264"},"PeriodicalIF":8.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674560/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216112","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":"Applications of ZIF-8-Based Nanoplatforms in Orthopedic Diseases: Evidence Base, Mechanistic Attribution, and Translational Barriers.","authors":"Tong Wu, Yan Wang, Xiaotian Feng, Benchao Dong, Peichuan Yang, Mengran Qin, Xiuguo Ge, Yimin Wang, JianXiong Ma","doi":"10.2147/IJN.S646799","DOIUrl":"10.2147/IJN.S646799","url":null,"abstract":"<p><p>Orthopedic diseases severely impair the quality of life of hundreds of millions of people worldwide and impose a substantial socioeconomic burden. Conventional treatments remain limited in terms of disease-site targeting, sustained drug release, and mitigation of adverse effects. Zeolitic imidazolate framework-8 (ZIF-8), formed through the coordination of Zn²⁺ with 2-methylimidazole, has a porous structure, a high cargo-encapsulation capacity, and environment-dependent disassembly characteristics. Through the release of Zn²⁺, it may also contribute to osteogenesis, antibacterial activity, and microenvironmental modulation. Accordingly, ZIF-8 has been investigated in preclinical studies of osteosarcoma, osteoporosis, osteoarthritis, osteomyelitis, and bone defect repair. Using a structured narrative and critical approach, this review summarizes strategies for ZIF-8 preparation, drug loading, and functionalization and compares the evidence across orthopedic indications with respect to research stage, validation of stimulus responsiveness, mechanistic attribution, biosafety, and barriers to clinical translation. Current evidence is derived primarily from in vitro and small-animal studies, and no therapeutic studies in humans have been identified. Although many studies have reported pH-dependent release in vitro, few have directly measured framework disassembly, cargo release, or Zn²⁺ exposure within disease sites in vivo. In multicomponent systems, the individual contributions of the therapeutic cargo, ZIF-8 framework, Zn²⁺, and surface modifications have rarely been adequately distinguished. Data on long-term toxicity, biodistribution, and clearance also remain limited, and batch-to-batch consistency and large-scale production have not been systematically validated. Future studies should prioritize formulation-specific physicochemical characterization and the establishment of safe dose windows. They should also include component controls that distinguish the contributions of the cargo, framework, and Zn²⁺, as well as clinically relevant comparators and large-animal models. These measures are needed to determine the incremental value and translational feasibility of ZIF-8 platforms for specific orthopedic indications.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"646799"},"PeriodicalIF":8.7,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671414/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216084","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":"Metal-Organic Framework-Based Nanomedicine for Sepsis Therapy: From Microenvironment Regulation to Precision Therapeutic Strategies.","authors":"Yesen Shou, Yukun Liu, Xuan Zhao, Zhikai Xu, Xiangjun Bai, Fangli Gao, Zhanfei Li, Yuchang Wang","doi":"10.2147/IJN.S639374","DOIUrl":"10.2147/IJN.S639374","url":null,"abstract":"<p><p>Sepsis is a complex and life-threatening syndrome driven by a dysregulated host response to infection, involving persistent oxidative stress, excessive inflammation, immune paralysis, metabolic disturbance, and progressive organ dysfunction. Although substantial advances have been achieved in supportive therapies, effective treatments capable of modifying the underlying pathological processes remain lacking. The major challenge lies in the highly interconnected nature of the septic microenvironment, where oxidative stress, inflammatory signaling, and immune imbalance form a dynamic pathological network that conventional single-target strategies cannot effectively correct. Metal-organic frameworks (MOFs) are crystalline porous materials assembled from metal nodes (eg, Fe, Cu, Ce, Mn, and Zn) and organic ligands; owing to their highly tunable structures, catalytic properties, and versatile cargo-loading capabilities, have recently emerged as promising nanoplatforms for addressing complex biological disorders. In sepsis therapy, MOFs provide unique opportunities not only for reactive oxygen species regulation and anti-inflammatory intervention but also for targeted drug delivery, immune modulation, pathogen/endotoxin neutralization, and integrated diagnosis and treatment. Key functionalization strategies reviewed here include enzyme-mimetic (nanozyme) catalysis, biomimetic membrane coating and active targeting, stimuli-responsive (pH/ROS) delivery, genetic cargo delivery, and theranostic integration. However, a systematic understanding of how MOF-based nanomedicine reshapes the multifaceted septic microenvironment remains insufficient. In this review, we summarize recent advances in MOF-based strategies for sepsis management, focusing on their roles in regulating oxidative stress, inflammatory responses, immune dysfunction, and metabolic abnormalities. We discuss the design principles of MOF nanoplatforms, including enzyme-mimetic catalysis, stimuli-responsive delivery, immune regulation, and theranostic applications. Furthermore, we highlight current challenges associated with biosafety (including the fate of released metal ions), pharmacokinetics, scalable fabrication, and clinical translation, and propose future perspectives involving precision nanomedicine and intelligent MOF design. This review aims to provide a comprehensive understanding of MOF-enabled regulation of septic pathological networks and to inspire the development of next-generation nanotherapeutic approaches for sepsis treatment.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"639374"},"PeriodicalIF":8.7,"publicationDate":"2026-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216154","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":"Stimulator of Interferon Genes (STING) Agonist-Loaded Copper-Based Nanoparticles for B7-H3 Blockade-Enhanced Chemodynamic-Immunotherapy of Ovarian Cancer.","authors":"Yuemei Jin, Jing Li, Qi Li, Shunqing Zhou","doi":"10.2147/IJN.S640431","DOIUrl":"10.2147/IJN.S640431","url":null,"abstract":"<p><strong>Introduction: </strong>Ovarian cancer remains difficult to treat because of limited tumor immunogenicity, poor cytotoxic T-cell infiltration, and a strongly immunosuppressive tumor microenvironment.</p><p><strong>Methods: </strong>Characterization, in vitro cell experiments, and tumor mouse model was performed.</p><p><strong>Results: </strong>Here, we developed an anti-B7-H3 antibody-modified, STING agonist-loaded copper-based nanoplatform for tumor-targeted chemodynamic-immunotherapy. The copper-containing nanoparticles enabled efficient loading of the non-nucleotide STING agonist MSA-2 and exhibited acid-responsive release of both MSA-2 and copper ions. Reactive oxygen species generation and intracellular glutathione depletion amplify oxidative stress, induce tumor-selective cytotoxicity, and trigger immunogenic cell death, as evidenced by increased release of ATP and HMGB1. Surface conjugation with anti-B7-H3 antibody preserved B7-H3-blocking activity and enhanced nanoparticle uptake, intracellular copper delivery, tumor accumulation in ovarian cancer cells. In vivo, the nanoplatform produced the strongest tumor-growth inhibition and significantly prolonged survival compared with non-targeted or single-component formulations. MSA-2 delivery was associated with enhanced STING pathway activation, increased inflammatory cytokine production, and improved antitumor immune responses, while anti-B7-H3 antibody modification promoted tumor accumulation. Importantly, the nanoplatform showed favorable biocompatibility, with no evident body-weight loss, major-organ injury, hematological abnormalities, or hepatic and renal dysfunction.</p><p><strong>Conclusion: </strong>This multifunctional nanoplatform integrates B7-H3-mediated tumor targeting and immune blockade, copper-based chemodynamic therapy, immunogenic cell death, and STING activation, providing a promising strategy for remodeling the ovarian tumor immune microenvironment and enhancing systemic antitumor immunity.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"640431"},"PeriodicalIF":8.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193437","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":"Nanocarrier-Integrated Topical Dosage Forms for Biofilm-Infected Wounds: Balancing Wound Retention, Biofilm Matrix Penetration, and Translational Feasibility.","authors":"Sri Agung Fitri Kusuma","doi":"10.2147/IJN.S643386","DOIUrl":"10.2147/IJN.S643386","url":null,"abstract":"<p><p>Biofilm-infected wounds are difficult to treat because extracellular polymeric substance (EPS) matrices, wound exudate, polymicrobial spatial organization, impaired antimicrobial penetration, persistent inflammation, and antimicrobial tolerance limit the efficacy of conventional topical therapy. Nanocarriers can protect antimicrobial payloads, enable controlled and stimuli-responsive release, and improve interactions with biofilm matrices; however, their clinical performance also depends on the final topical dosage form that governs wound residence, local exposure, usability, and translation. This review critically examines nanocarrier-integrated topical dosage forms for biofilm-infected wounds by linking nanoscale carrier design with macroscale platform performance. Hydrogels and in situ gels, films, membranes, wound dressings, nanofibers, sprays, foams, and multifunctional systems are discussed in relation to wound retention, exudate management, EPS access, and controlled antimicrobial release. Key strategies, including pH-, enzyme-, ROS-, and light-responsive delivery, EPS disruption, matrix penetration, photothermal and photodynamic therapy, ion-mediated killing, quorum-sensing interference, and wound-adaptive regenerative support, are integrated with translational considerations such as polymicrobial biofilm models, cytocompatibility, recurrence prevention, sterilization, storage stability, manufacturing scalability, regulatory classification, and patient-centered usability. By bridging nanocarrier engineering with topical dosage-form design, this review provides a formulation-oriented roadmap for clinically feasible antibiofilm nanomedicine for chronic and infected wounds, supporting control of infectious diseases, healthcare innovation, and sustainable manufacturing considerations.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"643386"},"PeriodicalIF":8.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665683/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193364","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":"Biodegradable ROS-Responsive TPCD Nanoparticles Mitigate Cisplatin-Induced Acute Kidney Injury via Synergistic Antioxidant and Immunomodulatory Actions.","authors":"Qin Wang, Wenrui Zhen, Zhouke Tan, Xiaoyong Yan, Bo Wang, Tao Pu, Zheng Cai, Yingsong Mu, Yu Ni, Xue Zhou, Juan Xu, Qi Liu","doi":"10.2147/IJN.S625338","DOIUrl":"10.2147/IJN.S625338","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) is a serious condition with high incidence and mortality rates, yet effective clinical treatment options remain limited. The therapeutic efficacy of small-molecule antioxidants such as N-acetylcysteine (NAC) is limited by their difficulty in targeting the kidneys and their rapid clearance. Nanomedicine platforms capable of simultaneously scavenging reactive oxygen species (ROS) and modulating inflammation offer new hope for the treatment of AKI.</p><p><strong>Methods: </strong>We employed a previously reported TPCD conjugate (β-cyclodextrin co-functionalized with Tempol and phenylboronic acid pinacol ester), which self-assembles into nanoparticles (TPCD NPs). Its ROS-scavenging, anti-inflammatory, and cytoprotective activities were evaluated in vitro. In a cisplatin-induced AKI mouse model, TPCD NPs were administered intravenously, and their efficacy was compared with that of NAC. Renal function (serum creatinine, BUN), histopathology, tubular apoptosis, inflammatory cytokines (TNF-α, IL-6), and macrophage polarization were assessed. In vivo fluorescence imaging was used to monitor their biodistribution and assess short-term safety.</p><p><strong>Results: </strong>TPCD NPs effectively scavenged ROS, reduced apoptosis, and suppressed inflammatory responses in vitro. In vivo, TPCD NPs significantly lowered serum creatinine and BUN levels, attenuated tubular injury and apoptosis, and decreased renal TNF-α and IL-6 levels compared with the model group and, in several endpoints, with NAC. The nanoparticles promoted macrophage polarization toward the reparative M2 phenotype. Fluorescence imaging revealed increased accumulation in injured kidneys, although renal retention was relatively short. Biocompatibility studies indicated acceptable short-term tolerability.</p><p><strong>Conclusion: </strong>TPCD NPs demonstrate renoprotective effects in cisplatin-induced AKI, likely via combined antioxidant, anti-apoptotic, and immunomodulatory actions. However, the observed renal accumulation requires further quantitative pharmacokinetic validation, and long-term safety and efficacy in other AKI models remain to be established. This study suggests that TPCD NPs are a promising preclinical candidate for AKI, but clinical translation claims should be made with caution.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"625338"},"PeriodicalIF":8.7,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193373","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 Protease-Responsive and Protein-Gated Gold Nanocluster Platform for Non-Invasive Urinary Colorimetric Diagnosis of Glioblastoma.","authors":"Ji Yang, Xianxian Liu","doi":"10.2147/IJN.S615554","DOIUrl":"https://doi.org/10.2147/IJN.S615554","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma multiforme (GBM) diagnosis remains challenging because conventional imaging may have limited ability to distinguish tumor progression or recurrence from treatment-related changes, and robust non-invasive biomarkers are still lacking. This study developed a protease-responsive gold nanocluster platform for urinary colorimetric detection of GBM via a synthetic biomarker strategy.</p><p><strong>Methods: </strong>We synthesized glutathione-capped AuNCs (GSH-AuNCs) and conjugated them with a substrate-responsive peptide (SRP) and a bulky NeutrAvidin (NAv) protein to form the AuNC-SRP-NAv complex. The NAv acts as a steric shield to lock the peroxidase-like activity of the AuNCs. The complex's physicochemical properties, stability, and protease-triggered activation (MMP-9) were characterized. In vivo biodistribution, renal clearance, and diagnostic performance were evaluated in orthotopic GBM-bearing mice.</p><p><strong>Results: </strong>The AuNC-SRP-NAv complex (diameter ~18.6 nm) exhibited robust stability and a signal-off state in systemic circulation. Upon encountering GBM-overexpressed MMP-9, the SRP was cleaved, releasing ultra-small AuNC fragments (<6 nm) that rapidly translocated to the urine. In tumor-bearing mice, these urinary AuNCs catalyzed the oxidation of TMB, producing a distinct blue color change within 20 minutes, while healthy controls showed no significant signal. Long-term safety assays (35 days) confirmed excellent biocompatibility with no systemic toxicity.</p><p><strong>Conclusion: </strong>The AuNC-SRP-NAv platform provides a simple, rapid, and non-invasive liquid biopsy approach for GBM. By integrating nanozyme catalysis with protease-responsive renal clearance, this system offers a promising alternative for early-stage tumor monitoring at the point of care.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"615554"},"PeriodicalIF":8.7,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181832","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}