International Journal of Nanomedicine最新文献

{"title":"Thymoquinone-Loaded Hexosomal Nanoparticles Attenuate Neuroinflammation and Improve Cognitive Function in an Alzheimer's Disease Mouse Model.","authors":"Nermin Eissa, Jana K Alwattar, Petrilla Jayaprakash, Haya Al Assaly, Roua Kharnoub, Aya Abed Altaleb, Khaloud Atif, Mohamad Rahal, Bassem Sadek","doi":"10.2147/IJN.S627692","DOIUrl":"10.2147/IJN.S627692","url":null,"abstract":"<p><strong>Introduction: </strong>Alzheimer's disease (AD) involves neuroinflammation that worsens cognitive decline. Thymoquinone (TQ) has potent anti-inflammatory activity, but its therapeutic application is limited by poor solubility, stability, and systemic bioavailability, which may restrict effective brain exposure. This study developed TQ-loaded hexosomal nanoparticles (TQ-HNP) to enhance TQ delivery and therapeutic efficacy in a dizocilpine (MK-801)- induced mouse model of AD.</p><p><strong>Methods: </strong>TQ-HNP were prepared using glyceryl monooleate, oleic acid, and poloxamer 407, optimized to ~104 nm size, -31 mV zeta potential, and ~95% entrapment efficiency. Following intraperitoneal administration of free TQ and TQ-HNP, male C57BL/6 mice treated with dizocilpine received intraperitoneal injections of free TQ or TQ-HNP and were subsequently evaluated for cognitive function (Novel Object Recognition test), anxiety-like behavior (Open Field test), and brain levels of the pro-inflammatory cytokines IL-6, TNF-α, and IL-1β.</p><p><strong>Results: </strong>Dizocilpine impaired memory and increased anxiety-like behavior in assessed mice, while TQ-HNP significantly improved both outcomes compared to free TQ. TQ-HNP also reduced IL-6 in the hippocampus and cerebellum and lowered TNF-α and IL-1β in the cerebellum, confirming its anti-inflammatory efficacy.</p><p><strong>Discussion: </strong>TQ-HNP enhanced the brain delivery of thymoquinone, mitigated neuroinflammation, and restored cognitive function in the AD-like mouse model, supporting its potential as a nanocarrier-based therapeutic strategy for Alzheimer's disease and other neurodegenerative disorders.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"627692"},"PeriodicalIF":8.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149220229","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":"Lactoferrin-Modified Ultra-Sustained Release Propofol Nanoparticles for Multi-Pathway Therapy of Depression via Intraperitoneal Injection.","authors":"Zhenyi Wu, Junze Deng, Shunlian Li, Lu Yu, Hang Zhang, Yufeng Xun, Jing Bian, Jing Liu, Jianbo Zhang, Pu Lei, Qingyan Ma, Yajuan Fan, Zai Yang, Feng Zhu, Xiancang Ma, Daocheng Wu, Shuo Zhang","doi":"10.2147/IJN.S645818","DOIUrl":"10.2147/IJN.S645818","url":null,"abstract":"<p><strong>Background: </strong>Depression imposes a significant burden on global public health, and traditional antidepressants are limited by slow onset, low efficacy, and high recurrence rates. Intraperitoneal injection of propofol can rapidly exert anti-anhedonic effects by regulating the VTA-NAc dopaminergic and GABAergic signaling pathways. However, its application in depression treatment is limited by rapid systemic clearance, poor brain permeability, and significant systemic toxicity. Moreover, the simple lipophilic structure of propofol and the limited drug-loading and long-term controlled-release performance of conventional physically encapsulated nanocarriers hinder the development of long-acting propofol formulations.</p><p><strong>Methods: </strong>Lactoferrin-functionalized PVA-propofol nanoparticles (LF-PVA@Pro NPs) were prepared based on the strong intermolecular affinity between PVA and propofol, as validated by molecular dynamics simulations. Their physicochemical properties, in vitro release behavior, brain-targeting efficiency, biosafety, and in vivo antidepressant efficacy were systematically characterized using CRS-induced depressive mouse models through multiple behavioral and histological assessments.</p><p><strong>Results: </strong>LF-PVA@Pro NPs achieved a drug loading of 19.3% and exhibited sustained in vitro release for 100 h. Following intraperitoneal injection, the formulation maintained therapeutic brain concentrations for 100 h (6-8-fold longer than free propofol) and increased cerebral drug accumulation by 2.5-fold. Its LD50 was 2802 mg/kg, 2.36-fold higher than that of free propofol, ensuring safety at the therapeutic dose of 40 mg/kg. In vivo studies demonstrated that LF-PVA@Pro NPs markedly alleviated depressive- and anxiety-like phenotypes, reduced VTA/NAc neuronal injury, and restored c-Fos, GABA, and DAT expression, thereby reactivating reward circuits.</p><p><strong>Conclusion: </strong>LF-modified ultra-sustained brain-targeted nanoparticles enable multi-pathway long-term depression intervention, offering a translatable strategy to repurpose propofol as a rapid-onset antidepressant for chronic stress-related depression.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"645818"},"PeriodicalIF":8.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13678437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149224046","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":"Osteosarcoma Nanomedicine: From Resistance Reversal to Bone Reconstruction.","authors":"Zhi Zheng","doi":"10.2147/IJN.S642747","DOIUrl":"10.2147/IJN.S642747","url":null,"abstract":"<p><p>The clinical management of Osteosarcoma (OS) is primarily hindered by two major challenges: intractable multidrug resistance and the reconstruction of critical-sized post-surgical bone defects. Nanomedicine provides a promising paradigm to overcome these clinical limitations. Synthesizing over 100 pivotal studies published predominantly between 2021 and 2026, this review moves beyond treating OS nanotherapy and bone tissue engineering as independent fields, conceptualizing them instead as a contiguous clinical pipeline. We map the trajectory of nanoscale interventions based on OS-specific biological barriers: progressing from systemic targeted nanotherapies designed to dismantle multidrug resistance and metabolic vulnerabilities (eg, ferroptosis, cuproptosis), to the localized management of the post-resection defect. Concurrently, we highlight the evolution of skeletal reconstruction through 3D-printed, stimuli-responsive biomimetic scaffolds. These smart implants exploit the unique OS microenvironment to precisely synchronize the eradication of residual microscopic disease with osteoinductive tissue regeneration. However, unpredictable in vivo degradation and chronic toxicity remain critical translational bottlenecks. Future breakthroughs demand artificial intelligence-guided predictive design and a paradigm shift from pure cytotoxicity toward immunomodulatory architectures that facilitate host-driven tumor clearance and bone regeneration.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"642747"},"PeriodicalIF":8.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216212","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":"Autophagy-Modulating Nanomedicine for Glioma: Delivery Barriers, Lysosomal Interactions, and a Flux-Resolved Translational Decision Framework.","authors":"Yiwei Liu, Jing Yang, Dongni Liang, Xiaohe Tian","doi":"10.2147/IJN.S637982","DOIUrl":"10.2147/IJN.S637982","url":null,"abstract":"<p><p>Glioma nanomedicine is constrained by linked delivery and pharmacodynamic barriers: nanoscale systems must traverse heterogeneous blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) interfaces and achieve interpretable intracellular effects in tumor cells. Autophagy is a therapeutically relevant but context-dependent axis. However, similar changes in static autophagy markers, vesicular staining, or ultrastructure can reflect productive autophagy induction (ie, increased autophagic flux with successful lysosomal cargo degradation), blocked autophagosome-lysosome fusion, lysosomal dysfunction, or secondary cytotoxic stress. This ambiguity is amplified for nanomedicines because their physicochemical properties can independently shape autophagy-related readouts. Here, we frame autophagy-modulating nanomedicine for glioma as both a delivery challenge and a problem of translational interpretation, covering bioactive nanomaterials, nanocarriers, and multimodal platforms. We organize the field around an integrated framework linking BBB/BBTB access, intracellular trafficking, interpretation of autophagic flux, and translational readiness. We use structured evidence grading to distinguish flux-resolved, functionally validated mechanisms from marker-based or indirect inferences. This framework distinguishes mechanistically supported findings from provisional interpretations and defines the evidence required for translational progression.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"637982"},"PeriodicalIF":8.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13674453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216138","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":"Peptide-Mediated Precise Intracellular Delivery of Bioactive Substances.","authors":"Qiancheng Gu, Jiao Lv, Yiling Zhang, Sergei Krasny, Lanjie Lei, Qiujie Li, Liyun Shi","doi":"10.2147/IJN.S640094","DOIUrl":"10.2147/IJN.S640094","url":null,"abstract":"<p><p>In the era of precision medicine, the site-specific delivery of biomacromolecular therapeutics, including nucleic acids and proteins, has emerged as a promising strategy for treating complex diseases. However, clinical translation of these therapeutics remains hindered by major physiological barriers, including inefficient translocation across cell membranes, endosomal/lysosomal entrapment and subsequent degradation, and inadequate targeting of specific subcellular organelles. Peptides have emerged as versatile functional modules for intracellular delivery owing to their programmable sequences and tunable biological functions. Although previous reviews have focused primarily on individual aspects of peptide-based delivery, particularly cell-penetrating peptides, peptide-drug conjugates, or peptide-functionalized nanocarriers, a systematic overview encompassing the entire intracellular delivery cascade remains lacking. This review summarizes recent advances in the peptide-mediated precise delivery of bioactive substances, with particular emphasis on the mechanisms underlying cell-specific targeting, membrane translocation, endosomal escape, and subsequent delivery of bioactive molecules to specific subcellular organelles, including the nucleus, mitochondria, and endoplasmic reticulum. Key design strategies are discussed, including the covalent conjugation of peptides to therapeutic payloads, supramolecular self-assembly, and the modular integration of multifunctional peptide units with stimuli-responsive nanocarriers. We further highlight recent applications of peptide-mediated precision delivery systems in cancer therapy, gene therapy, neurological diseases, infectious disease control, and diagnostic imaging. Finally, we discuss the major challenges limiting the clinical translation of these systems and identify potential directions for future research. By integrating these advances into a framework for peptide-based precision delivery, this review aims to provide a conceptual foundation for the development and clinical translation of next-generation therapeutic delivery systems based on programmable, targeted, and controllable peptide functionalities.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"640094"},"PeriodicalIF":8.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13676037/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149216218","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":"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}