International Journal of Nanomedicine最新文献

{"title":"Combating Bacterial Infection with Metabolism-Regulating Nanomaterials.","authors":"Danqing Yu, Qionghong Ma, Bangxun Mao, Songping Yu, Yanni Song, Chunhui Dai, Dongliang Yang, Xuyang Chen","doi":"10.2147/IJN.S636550","DOIUrl":"https://doi.org/10.2147/IJN.S636550","url":null,"abstract":"<p><p>The rise of antibiotic resistance presents a major global health challenge. Bacterial survival is closely tied to their metabolic reprogramming under stress, which enhances their environmental adaptability. While current antibacterial strategies are often limited by bacterial resistance, nanomaterials offer a promising alternative due to their unique physicochemical properties. These functionalized nanoagents can precisely deliver antimicrobials and selectively interfere with metabolic processes of bacteria, including aerobic and anaerobic metabolism, peptidoglycan synthesis, metal ion homeostasis, and nitrogen metabolism. By interfering with energy metabolism, nutrient uptake, and quorum sensing, they can effectively eliminate drug-resistant and persister bacteria. In this review, we summarize the recent advances in metabolic-regulating antibacterial treatment. Then, the clinical translation challenges facing nanotechnology-driven metabolic regulation strategies are discussed. Finally, we hope this review offers forward-looking perspectives on the development of non-antibiotic antibacterial nanoagents for future bacterial metabolic interventions.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"636550"},"PeriodicalIF":8.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900335","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":"Nanotherapeutic Strategies for MASLD: From Pathological Mechanisms to Targeted Delivery Systems.","authors":"Na Li, Dongqi Zhou, Fanghang Ye, Fei Yu, Liyuan Hao, Shenghao Li, Qing Peng, Jiali Deng, Xiaoyu Hu","doi":"10.2147/IJN.S631025","DOIUrl":"https://doi.org/10.2147/IJN.S631025","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a progressive metabolic liver disorder driven by hepatic lipid overload, oxidative stress, mitochondrial dysfunction, innate immune activation, insulin resistance, gut-liver axis dysregulation, and liver fibrosis. These interconnected pathological processes involve hepatocyte injury, macrophage-mediated inflammation, liver sinusoidal endothelial cell dysfunction, hepatic stellate cell activation, and extracellular matrix deposition. However, conventional therapeutic agents are often limited by poor solubility, insufficient stability, low intrahepatic exposure, nonspecific distribution, and inadequate target-cell selectivity. Nanoparticle-based delivery systems may overcome these limitations by improving drug stability, hepatic accumulation, controlled release, and cell-specific delivery. This review summarizes recent advances in nanotherapeutic strategies for MASLD from three complementary perspectives: intervention in key pathological processes, cell-specific delivery to major hepatic cell populations, and the design characteristics of different nanoplatforms. We discuss nanodelivery strategies targeting lipid metabolic dysfunction, oxidative injury, inflammation, insulin resistance, gut-liver axis dysfunction, and fibrogenesis, as well as delivery approaches directed at hepatocytes, hepatic stellate cells, liver macrophages, and liver sinusoidal endothelial cells. Multicellular co-delivery strategies for modulating pathological crosstalk are also considered. In addition, we compare the advantages and limitations of inorganic nanoparticles, polymeric nanoparticles, liposomes and other lipid-based nanosystems, and bio-derived or biomimetic nanocarriers. Particular attention is given to how carrier composition, physicochemical properties, surface functionalization, and release behavior can be matched with therapeutic cargoes, target cells, and pathological processes. Although these platforms provide opportunities for multi-process and cell-specific intervention in MASLD, most evidence remains preclinical. Major barriers to clinical translation include long-term safety, controllable biodistribution, differences between experimental models and human disease, scalable manufacturing, batch-to-batch consistency, and standardized quality evaluation. Addressing these issues during nanoplatform design and assessment will be essential for translating targeted nanodelivery systems into clinically applicable therapies for MASLD.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"631025"},"PeriodicalIF":8.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546670/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900309","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":"Chlorogenic Acid in Antitumor Therapy: Multi-Pathway Mechanisms, Nanocarrier-Mediated Smart Delivery, and Synergistic Combinatorial Strategies.","authors":"Huijuan Duan, Juan He, Rui Wang, Jie Wu, Haitao Ding","doi":"10.2147/IJN.S627003","DOIUrl":"https://doi.org/10.2147/IJN.S627003","url":null,"abstract":"<p><p>Malignant tumors remain a global public health challenge with high morbidity and mortality. Conventional therapies are limited by severe adverse effects and drug resistance. Chlorogenic acid (CGA), a widely distributed phenolic compound, has emerged as a promising antitumor agent due to its excellent biocompatibility and multi-targeted bioactivities, including antioxidant, anti-inflammatory, immunomodulatory, and pro-apoptotic. This review systematically summarizes the molecular mechanisms underlying the antitumor activity of CGA, focusing on three core aspects: (1) regulation of key signaling pathways (Janus kinase-signal transducer and activator of transcription (JAK-STAT), Mitogen-Activated Protein Kinase (MAPK), Nuclear factor kappa-B (NF-κB)) in tumor cells; (2) enhancement of host antitumor immune function through immune‑cell activation and cytokine‑network modulation; and (3) induction of tumor cell apoptosis via B-cell lymphoma 2 (Bcl-2) family regulation, oxidative stress, and metabolite synergy. Furthermore, we highlight recent advances in nanocarrier-facilitated delivery of CGA, including metal-based nanocomposites, metal oxide nanoparticles, and functionalized liposomes, and establish a horizontal comparison table to analyze their respective delivery efficiency, tumor accumulation, biosafety and immune activation capacity, which effectively overcome its pharmacokinetic shortcomings, such as short circulation half‑life and poor tumor accumulation. Additionally, synergistic antitumor effects achieved by combining CGA with chemotherapy drugs or immune checkpoint inhibitors across melanoma, lung cancer, colon cancer and hepatocellular carcinoma models are comprehensively discussed. This review provides a comprehensive theoretical foundation for the further development of CGA as a promising antitumor agent and its clinical translation, and outlining operable key challenges and future research directions.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"627003"},"PeriodicalIF":8.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546656/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900393","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":"Lymph Node-Targeted PLGA-EgG1Y162 Nanovaccine for Synergistic Immunity Against <i>Echinococcus granulosus</i> Infection.","authors":"Mayire Aizezi, Ayinula Tuohetali, Mutailipu Maimaiti, Xuan Li, Ya Song, Xia Chen, Guangfeng Chen, Saifuding Abula, Huijing Gao, Ruofeng Yan, Kalibixiati Aimulajiang","doi":"10.2147/IJN.S620325","DOIUrl":"https://doi.org/10.2147/IJN.S620325","url":null,"abstract":"<p><strong>Background: </strong>Cystic echinococcosis (CE), a zoonosis caused by <i>Echinococcus granulosus</i>, severely endangers human and animal health in western pastoral China. Conventional surgery and chemotherapy suffer from high recurrence and toxic side effects, so immunization is urgently needed for CE prevention.</p><p><strong>Methods: </strong>We constructed a PLGA nanovaccine loading EgG1Y162 antigen (PLGA-EgG1Y162) via double emulsion-solvent evaporation. Its physicochemical features, DC activation, in vivo lymph node retention, immune response, anti-infection protection and CD4⁺ T cell transcriptome were comprehensively detected.</p><p><strong>Results: </strong>The nanovaccine showed uniform spherical morphology with an average particle size of 394 nm and 79% encapsulation efficiency, presenting favorable sustained-release performance and excellent biocompatibility. In vitro experiments verified that PLGA-EgG1Y162 was efficiently taken up by dendritic cells and effectively facilitated DC maturation. In vivo tracking demonstrated that the nanovaccine achieved prolonged retention within lymph nodes. Compared with the free antigen group and Freund's adjuvant-adjuvanted group, PLGA-EgG1Y162 induced significantly higher and longer-lasting antigen-specific IgG antibodies, markedly upregulated splenic IFN-γ, IL-4, IL-10 and TNF-α expression, and maintained elevated proportions of splenic CD4⁺ and CD8⁺ T cells. At 16 and 24 weeks post infection, vaccinated mice had remarkably fewer hepatic cysts, reduced liver-to-body weight ratios and lower serum transaminase levels, with relatively intact hepatic tissue architecture. Transcriptomic data illustrated that the vaccine reshaped CD4⁺ T cell transcriptional profiles, alleviated infection-triggered chronic inflammation, and suppressed aberrant activation of hepatic autophagy-related genes.</p><p><strong>Conclusion: </strong>PLGA-EgG1Y162 realizes lymph node-targeted sustained antigen delivery to elicit balanced long-lasting humoral and cellular immunity, producing prominent protection against <i>E. granulosus</i>. This work offers a promising immunoprophylactic candidate for cystic echinococcosis.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"620325"},"PeriodicalIF":8.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900338","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":"Nanomedicine-Empowered CAR-T Therapy for Multiple Myeloma: Toward Programmable, Durable, and Precision Immunotherapy.","authors":"Can Huang, Xuyan Zhang, Yuanyin Teng, Zhongsong Zhang, Bing Wang, Panpan Gu, Xiang Deng, Dianwen Wang, Hongli Xiao, Lingli Zou, Meng Zhao, Caifeng Zheng, Gaochun Zeng, Jianyun Li, Zoufang Huang","doi":"10.2147/IJN.S628321","DOIUrl":"https://doi.org/10.2147/IJN.S628321","url":null,"abstract":"<p><p>Multiple myeloma (MM) remains a difficult-to-cure hematologic malignancy. Although B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR-T) therapy has substantially deepened clinical responses in patients with relapsed/refractory MM, its broader clinical application remains constrained by post-treatment relapse, insufficient response durability, prolonged manufacturing timelines, and limited accessibility. Increasing evidence indicates that relapse after CAR-T therapy in MM arises not from a single mechanism but from the convergence of tumor antigen remodeling, CAR-T cell exhaustion, impaired metabolic fitness, and bone marrow microenvironment-mediated immunosuppression. Nanomedicine provides modular engineering strategies to address these interconnected barriers to therapeutic efficacy. For example, lipid nanoparticles, polymeric carriers, biomimetic nanoplatforms, and targeted delivery systems may optimize ex vivo CAR-T manufacturing, enable in vivo CAR-T cell generation, regulate BCMA antigen density, remodel the bone marrow niche, and facilitate dynamic monitoring of relapse risk. This review systematically examines the major biological mechanisms underlying relapse after CAR-T therapy in MM, with particular emphasis on both the therapeutic potential of nanotechnology and the translational challenges associated with CAR-T manufacturing optimization, in vivo immune programming, bone marrow microenvironment remodeling, and relapse control in the post-BCMA era. By integrating advances in tumor immunology, materials science, and hematologic oncology, this review proposes a conceptual framework and future research priorities for developing faster, more controllable, durable, and accessible CAR-T therapeutic strategies for MM.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"628321"},"PeriodicalIF":8.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900333","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":"Nanodrug Delivery Systems for Lower Respiratory Infections: Pulmonary Targeting, Anti-Infective Applications, and Translational Challenges.","authors":"Wen-Bin Zhu, Ting Liu, Guang-Liang Cheng, Kai-Qian Xu, Jun-Mei Fang, Ying Ma, Jin-Xia Lu, Yi Xue, Ling-Ling Xu","doi":"10.2147/IJN.S623071","DOIUrl":"https://doi.org/10.2147/IJN.S623071","url":null,"abstract":"<p><p>Lower respiratory infections (LRIs) remain a leading cause of global morbidity and mortality, particularly among vulnerable populations such as children and the elderly. Although conventional antimicrobial therapies remain central to clinical management, their efficacy is often limited by poor pulmonary bioavailability, systemic toxicity, inadequate penetration of mucus or biofilms, and the rapid emergence of drug-resistant pathogens. Nanodrug delivery systems (NDDS) provide a promising strategy to address these limitations by improving pulmonary deposition, protecting labile therapeutics, enabling controlled release, and supporting disease-site targeting. In this review, we systematically summarize recent advances in NDDS for LRIs, with emphasis on the design principles and functional characteristics of lipid-based, polymeric, inorganic, and hybrid nanocarriers. We further connect these platforms with disease-specific therapeutic challenges in bacterial pneumonia, tuberculosis, viral infections, and fungal pneumonia, highlighting how carrier composition, surface engineering, and release behavior can be adapted to mucus barriers, biofilms, intracellular pathogen niches, and inflammatory microenvironments. Importantly, we discuss emerging trends, including bioinspired nanocarriers, stimuli-responsive systems, and multifunctional theranostic platforms, while also evaluating key translational barriers such as biosafety, immunogenicity, reproducible manufacturing, and regulatory standardization.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"623071"},"PeriodicalIF":8.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900384","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":"Smart Colloidal Systems as Drug Delivery and Therapeutic Modulation Platforms for Renal Cell Carcinoma.","authors":"Liming Sun, Xinming Zhao, Xiaoting Li, Zhanmeng Zhu, Guangzhen Wu","doi":"10.2147/IJN.S590442","DOIUrl":"https://doi.org/10.2147/IJN.S590442","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC) is one of the major malignant tumors of the genitourinary system and remains difficult to treat in advanced or recurrent settings. Although surgery, antiangiogenic targeted therapy, immune checkpoint blockade, mTOR inhibition, and HIF-2α-targeted therapy have improved clinical outcomes, recurrence, therapeutic resistance, heterogeneous tumor exposure, and systemic toxicity continue to restrict long-term efficacy. Smart colloidal systems have attracted attention as drug delivery and therapeutic modulation platforms because their size, surface properties, composition, and responsiveness can be engineered to improve drug stability, tumor accumulation, intracellular delivery, and controlled release. In this review, \"smart colloidal systems\" refers to functionally engineered colloidal platforms whose design confers therapeutic behavior beyond passive drug encapsulation, including selective tumor- or cell-directed delivery, controlled or stimulus-triggered release or activation, enhanced intracellular delivery, intrinsic carrier-mediated biological effects, and coordinated multimodal therapy. In RCC, these systems have been explored for the delivery of tyrosine kinase inhibitors, immune agonists, checkpoint-regulating nucleic acids, therapeutic genes, siRNAs, ferroptosis-inducing agents, photosensitizers, sonosensitizers, and combination regimens. This review summarizes recent progress in smart colloidal systems for RCC therapy from a treatment-modality perspective, including targeted therapy, immunotherapy, gene and RNA therapy, metabolic and ferroptosis-based therapy, externally triggered therapy, and combination treatment. However, most RCC-directed smart colloidal systems remain at the preclinical stage. Toxicity, renal safety, immune compatibility, biodistribution, manufacturing feasibility, and clinical translation are also discussed. By linking the delivered cargo, colloidal platform, biological rationale, and antitumor strategy, this review aims to clarify the potential value and limitations of smart colloidal systems in RCC treatment.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"590442"},"PeriodicalIF":8.7,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900387","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-Based Drug Delivery Systems for Periodontitis: Antibacterial, Immunomodulatory, and Regenerative Strategies.","authors":"Liyan Wang, Yanwei Chen, Lu Li, Deshi Dong","doi":"10.2147/IJN.S630550","DOIUrl":"https://doi.org/10.2147/IJN.S630550","url":null,"abstract":"<p><p>Periodontitis is a chronic inflammatory disease associated with obesity, type 2 diabetes, and cardiovascular disease, and has become a serious public health issue. Antibacterial treatment and mechanical debridement are the main treatment strategies for periodontitis. However, side effects and bacterial resistance might lead to treatment failure. Nanotechnology systems have new opportunities for the management of periodontitis. With benefits including superior targeting and fewer side effects, drug delivery systems constructed with nanoparticles (NPs) may provide local, delayed, and regulated drug release. When combined with immunomodulatory therapy, tissue regeneration, and antibacterial therapy, a high drug loading capacity of individual medications or therapeutic combinations is made possible by the large surface area to volume ratio of nanoparticles, providing synergistic beneficial effects. This paper reviews the progress in the research and application of nanoparticle-based drug delivery systems in the treatment of periodontitis. We focused on the pathophysiology of periodontitis, introduced the rational design of nano-drug delivery systems, and concentrated on the local approaches to treatment for periodontitis. Furthermore, the future challenges and research prospects for nanoparticle-based drug delivery systems in the treatment of periodontitis are also covered in this paper.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"630550"},"PeriodicalIF":8.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897297","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":"Depletion of Soluble PD-L1 with Engineered Nanoparticles Promotes Antitumor Immunity and Tumor Control.","authors":"Michelle A Hsu, Jacob B Hirdler, Roxane Lavoie, Jacob J Orme, Louis Hawthorne, Curtis L Ruegg, John Dodgson, Haidong Dong, Sean S Park, Fabrice Lucien","doi":"10.2147/IJN.S607073","DOIUrl":"https://doi.org/10.2147/IJN.S607073","url":null,"abstract":"<p><strong>Purpose: </strong>Programmed Cell Death Protein 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) checkpoint blockade has led to improvements in clinical outcomes for various advanced cancers. However, response rates remain low, and most patients present with intrinsic resistance to PD-1/PD-L1 inhibitors. Circulating soluble PD-L1 (sPD-L1) has emerged as a driver of resistance to PD-1/PD-L1 inhibitors. Elevated levels of sPD-L1 can be detected in peripheral blood in patients with cancer and are associated with poor prognosis and resistance to PD-1/PD-L1 therapy, highlighting the need to find strategies to remove sPD-L1 from circulation. Here, we evaluated the efficacy and immunological responses of using NaNots^®A, a type of engineered nanoparticle that has been designed to capture sPD-L1, as a therapeutic agent to treat cancer.</p><p><strong>Methods: </strong>Different biological samples containing sPD-L1 were tested pre- and post-treatment to determine the capturing efficiency of NaNots. To evaluate the therapeutic potential of NaNots in vivo, a humanized PD-L1 mouse model was used with an sPD-L1 secreting tumor model to assess tumor growth and to immunophenotype antitumor responses.</p><p><strong>Results: </strong>NaNot treatment successfully depleted sPD-L1 from multiple sources, including patient and mouse plasma. NaNot treatment resulted in substantial tumor growth delay and increased proportions of effector CD8 T cells, concurrent with decreased immunosuppressive regulatory T cells, in tumor and spleen tissues.</p><p><strong>Conclusion: </strong>Overall, this preclinical work demonstrates that selective capture of sPD-L1 in vivo with a novel nanotherapeutic platform can reduce immune suppression concurrent with greater immune activation, thereby enabling tumor growth control.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"607073"},"PeriodicalIF":8.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897292","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":"Research Progress on Tumor Microenvironment-Responsive siRNA Nanocarriers: Design Strategies, Delivery Efficiency, and Future Perspectives.","authors":"Xiaoxi Zhu, Gong Zhang, Lin Li, Puguang Yu, Peng Su, Hongyuan Liang, Dan Dong, Dongyan Liu, Kefeng Wang","doi":"10.2147/IJN.S616904","DOIUrl":"https://doi.org/10.2147/IJN.S616904","url":null,"abstract":"<p><p>Gene silencing by RNA interference (RNAi) has emerged as a promising strategy for cancer therapy. Small interfering RNA (siRNA), a class of small regulatory RNAs that recognize and degrade complementary target messenger RNAs (mRNAs) in a sequence-specific manner at the post-transcriptional level, plays a critical role in regulating gene expression. However, the in vivo delivery of siRNA remains a formidable challenge due to its poor physiological stability, susceptibility to enzymatic degradation, inability to efficiently cross cellular membranes, non-specific off-target effects, and immunostimulation. Overcoming these barriers and enhancing the gene silencing efficiency of siRNA in target cells is essential for the clinical translation of RNAi technology. In recent years, tumor microenvironment (TME)-responsive nanocarriers have attracted considerable attention as a strategy to improve siRNA stability, enhance its enrichment and penetration at tumor sites, facilitate cellular uptake, and promote efficient gene silencing. This review comprehensively summarized the design principles and functional characteristics of TME-responsive siRNA delivery nanocarriers, with a focus on five major stimuli: pH, hypoxia, enzymes, glutathione (GSH), and reactive oxygen species (ROS). We critically analyze the advantages and limitations of existing nanocarrier systems, provide comparative insights through summary tables, and discuss future directions including multi-stimuli-responsive systems, combination therapies, and clinical translation challenges. This review aims to provide a systematic framework for understanding and advancing TME-responsive siRNA nanocarriers for tumor therapy.</p>","PeriodicalId":14084,"journal":{"name":"International Journal of Nanomedicine","volume":"21 ","pages":"616904"},"PeriodicalIF":8.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13546063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148897357","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}