{"title":"Catalytic immunotherapy via ultrasmall Ir supported metal clusters on defect-engineered nanoplatforms for tumor metabolic disruption and enhanced immunogenic cell death","authors":"Liang Zhuang , Qinzong Gao , Lishi Chen , Xinyu Xiong , Yu Wei , Shan He , Dawei Li , Shanyue Guan , Hui Chen","doi":"10.1016/j.nantod.2025.102878","DOIUrl":"10.1016/j.nantod.2025.102878","url":null,"abstract":"<div><div>Immunogenic cell death (ICD) is a promising immunotherapy route, yet its efficacy is hampered by modest ICD induction and the hostile tumor microenvironment (TME). We engineer a multifunctional nanocatalyst (G@Ir/MnFe-MMO), with tailored MnFe-MMO nanosheets containing abundant oxygen vacancies (O<sub><em>v</em></sub>) that serve as anchoring sites for ultrasmall Ir-supported metal clusters (Ir-SMCs) and form Mn–O<sub><em>v</em></sub>–Fe electron bridges to facilitate directional electron transfer. This unique structural arrangement enhances catalytic activity by accelerating ROS generation at Ir-SMCs sites and enabling efficient NADH (reduced nicotinamide adenine dinucleotide) oxidation, thereby inducing redox disequilibrium and collapsing tumor metabolic homeostasis. Upon 808 nm laser irradiation, oxidative stress and the rapid NADH depletion collapses redox balance, depolarizes the mitochondrial membrane and drains adenosine triphosphate (ATP), provoking sustained endoplasmic reticulum (ER) stress that magnifies damage-associated molecular patterns (DAMPs) release and strengthens ICD. Furthermore, the loaded lactate dehydrogenase A (LDHA) inhibitor GNE-140 quenches lactate production and blocks NAD<sup>+</sup> (oxidized nicotinamide adenine dinucleotide) regeneration, ultimately relieving TME-driven immunosuppression and enhancing the persistence and activity of inflammatory immune cells within TME. Consequently, G@Ir/MnFe-MMO not only induces potent ICD but also enhances tumor immune infiltration and systemic antitumor responses, leading to significant suppression of both primary and distant tumors <em>in vivo</em>. This strategy provides a compelling therapeutic paradigm for overcoming tumor metabolic plasticity and boosting the clinical efficacy of ICD-based tumor immunotherapy.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102878"},"PeriodicalIF":10.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-08-25DOI: 10.1016/j.nantod.2025.102877
Zhe-Nan Liu , Li-Li Yu , Pan Liu , Han-Zhe Liu , Hui Zhao , Yun-Qing Sun , Lan Liu , Tong Wang , Xian-Zheng Zhang , Guo-Feng Luo , Zheng-Jun Shang
{"title":"Overcoming the p-EMT-mediated stromal barrier at the tumor periphery with hybrid membrane-camouflaged nanoplatform for enhanced chemotherapy","authors":"Zhe-Nan Liu , Li-Li Yu , Pan Liu , Han-Zhe Liu , Hui Zhao , Yun-Qing Sun , Lan Liu , Tong Wang , Xian-Zheng Zhang , Guo-Feng Luo , Zheng-Jun Shang","doi":"10.1016/j.nantod.2025.102877","DOIUrl":"10.1016/j.nantod.2025.102877","url":null,"abstract":"<div><div>Effective intratumoral penetration of nanotherapeutics is the prerequisite for successful cancer treatment. However, the dense tumor stroma often hinders deep drug penetration. In this work, we identified a previously overlooked physiological barrier at the leading edge of tumor nests, which was formed by the tumor cells undergoing partial epithelial-mesenchymal transformation (p-EMT). Adjacent cancer-associated fibroblasts (CAFs) promote this process through paracrine signaling, ultimately blocking nanoparticle penetration into the tumor interstitium. In light of this, we elaborately developed a tailored nanodrug, C/D-MOF<sub>HM</sub>, by camouflaging a curcumin (CUR)-based, doxorubicin (DOX)-loaded, metal-organic framework nanoparticle with a hybrid membrane derived from CAFs and tumor cells. The C/D-MOF<sub>HM</sub> selectively deliveres CUR to CAFs to inhibit the secretion of p-EMT-inducing factors (e.g., TGF-β1 and IL-6), thereby suppressing p-EMT-mediated stromal matrix formation at the tumor periphery. As a result, augmented drug penetration of C/D-MOF<sub>HM</sub> is evidently observed, leading to potent tumor growth inhibition and metastasis suppression. This p-EMT blockade strategy for diminishing the stromal barrier at tumor margins represents a feasible approach to improve drug penetration into solid tumors for enhanced tumor therapy.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102877"},"PeriodicalIF":10.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144893461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-08-21DOI: 10.1016/j.nantod.2025.102876
Huan Ye , Dongxiao Xu , Xiaochuan Zhang , Jing Yan , Yang Zhou , Mingxin Ye , Jianfeng Shen , Lichen Yin , Zhuchao Zhou
{"title":"One-pot solvothermal synthesis of polyvinyl pyrrolidone and ethylene glycol-modified Cu2SnS3 (PE/CTS) nanomaterials for photothermal immunotherapy","authors":"Huan Ye , Dongxiao Xu , Xiaochuan Zhang , Jing Yan , Yang Zhou , Mingxin Ye , Jianfeng Shen , Lichen Yin , Zhuchao Zhou","doi":"10.1016/j.nantod.2025.102876","DOIUrl":"10.1016/j.nantod.2025.102876","url":null,"abstract":"<div><div>Photothermal therapy (PTT) not only ablates tumor tissues, but also activates antitumor immunity by enhancing immunogenicity, which highly relies on photothermal nanoagents (PTNAs) with excellent photothermal effect. Herein, polyvinyl pyrrolidone (PVP) and ethylene glycol (EG)-modified Cu<sub>2</sub>SnS<sub>3</sub> (PE/CTS) nanoparticles (NPs) and nanosheets (NSs) with excellent biocompatibility and stability were synthesized <em>via</em> the one-pot solvothermal method and applied for photothermal immunotherapy. Because of their strong near-infrared (NIR) light absorption and high extinction coefficient, PE/CTS NPs and NSs possessed high photothermal conversion efficiency (PCE) of 39.3 % and 46.8 %, respectively. Furthermore, the superior photothermal effect of PE/CTS NPs over NSs in the NIR-I region was confirmed both <em>in vitro</em> and <em>in vivo</em>, mainly because of the longer blood circulation time, enhanced tumor accumulation, and higher tumor cell uptake level of NPs. As thus, PE/CTS NPs-mediated PTT effectively inhibited growth of 4T1 xenograft tumors in mice. Moreover, it enhanced local/systemic immune responses by inducing the maturation of dendritic cells (DCs) followed by the activation, proliferation, and intratumoral infiltration of T lymphocytes, and it alleviated immunosuppression by promoting the production of M1-phenotype macrophages and the reduction of regulatory T cells (Tregs). Consequently, PE/CTS NPs-mediated PTT notably inhibited the growth of distant tumors. This study highlights the potential of CTS-based nanomaterials for photothermal immunotherapy, broadening the scope of medical applications of ternary metal chalcogenide nanomaterials.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102876"},"PeriodicalIF":10.9,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144886240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-08-19DOI: 10.1016/j.nantod.2025.102871
Zhixiong Huang , Jiamin Zhang , Yuyan Qian , Hengxu Liu , Yufen Xiao , Jianzhong Du
{"title":"Antioxidant glycopolymersomes with dynamic covalent glucose regulation for synergistic pancreatitis-diabetes therapy","authors":"Zhixiong Huang , Jiamin Zhang , Yuyan Qian , Hengxu Liu , Yufen Xiao , Jianzhong Du","doi":"10.1016/j.nantod.2025.102871","DOIUrl":"10.1016/j.nantod.2025.102871","url":null,"abstract":"<div><div>Pancreatitis and diabetes mellitus are interconnected pathologies lacking integrated therapeutic strategies. Current insulin-based therapies risk exacerbating pancreatic inflammation, necessitating \"drug-free\" alternatives. Herein, we report the first dynamic covalent glycopolymersome platform engineered <em>via</em> reversible addition-fragmentation chain-transfer (RAFT) polymerization and macromolecular self-assembly to synergistically address both conditions. The glycopolymersomes, self-assembled from a triblock copolymer poly(ethylene oxide)-<em>block</em>-poly(4-acrylamidophenylboronic acid-<em>stat</em>-<em>N</em>-acryloyl glucosamine)-<em>block</em>-poly(aminoethyl methacrylate) [PEO-<em>b</em>-P(AAPBA-<em>stat</em>-AGA)-<em>b</em>-PAEMA], integrate glucose-responsive phenylboronic acid moieties for sustained blood glucose regulation and conjugated antioxidants (ferulic acid or tyrosine) for reactive oxygen species (ROS) scavenging. <em>In vitro</em> studies demonstrate reversible glucose responsiveness and potent ROS elimination. <em>In vivo</em>, these glycopolymersomes achieve 60 h of normoglycemia in type 1 diabetic mice and accumulate selectively in the pancreas, mitigating oxidative stress, inflammation, and edema in murine models. Overall, this work pioneers the use of dynamic covalent polymer architectures for dual metabolic regulation, offering a blueprint for insulin-free nanomedicine aimed at treating complex metabolic disorders.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102871"},"PeriodicalIF":10.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-08-19DOI: 10.1016/j.nantod.2025.102874
Siyu Tian , Qiaoya Zhao , Zhengxun Liu , Mudi Feng , Peina Wang , Yingying Guo , Linhao You , Yan-Zhong Chang
{"title":"The bifunctional nanomaterials of iron-chelating and antioxidant targeting the blood-brain barrier in the injured area alleviated cerebral ischemia-reperfusion injury","authors":"Siyu Tian , Qiaoya Zhao , Zhengxun Liu , Mudi Feng , Peina Wang , Yingying Guo , Linhao You , Yan-Zhong Chang","doi":"10.1016/j.nantod.2025.102874","DOIUrl":"10.1016/j.nantod.2025.102874","url":null,"abstract":"<div><div>Stroke is a major cause of morbidity and mortality in both developing and developed countries. After thrombolysis, oxidative stress and free iron levels in the area of brain injury rapidly increase, resulting in neural cell death via apoptosis and ferroptosis. Moreover, due to the limitations of the blood-brain barrier, most drugs cannot efficiently reach the injured area to treat the neurons in proximity to the injury. Here we describe nanoliposomes based on the damaged endothelial cell-targeting properties of platelets and the ability of rabies virus peptides to mediate penetration of the blood-brain barrier, carrying the natural antioxidant, lycopene, and the iron chelator, deferoxamine. After treatment with the nanomaterial, the brain injury area of ischemia-reperfusion mice was significantly reduced, and the apoptosis and ferroptosis of brain cells were remarkably improved. This dual-function, targeted nanoparticle represents a new approach for the treatment of stroke and other conditions related to neurological or peripheral ischemia-reperfusion injury.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102874"},"PeriodicalIF":10.9,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-08-18DOI: 10.1016/j.nantod.2025.102870
Shunfeng Wang , Xinxin Sun , Yi Li , Zhixiao Zhang , Jin Sun , Zhonggui He , Cong Luo , Shenwu Zhang
{"title":"Engineering immunomodulatory hydrogels for diabetic wound microenvironment reprogramming","authors":"Shunfeng Wang , Xinxin Sun , Yi Li , Zhixiao Zhang , Jin Sun , Zhonggui He , Cong Luo , Shenwu Zhang","doi":"10.1016/j.nantod.2025.102870","DOIUrl":"10.1016/j.nantod.2025.102870","url":null,"abstract":"<div><div>Diabetic wounds, characterized by impaired healing due to chronic inflammation and immune dysregulation, pose a significant clinical challenge. Traditional therapies often fail to address the complex immunological dysfunction underlying these wounds. Immunomodulatory hydrogels have become a promising therapeutic strategy for promoting macrophage polarization, inhibiting the formation of NETs, and effectively recruiting T cell. This review provides a comprehensive overview of recent advancements in immunoregulatory hydrogels for diabetic wound healing, focusing on their mechanisms of action, design principles, and clinical potential. Additionally, we explore the design principles of immunoregulatory hydrogels, including biomaterial selection, crosslinking strategies, and active drug integration. Finally, we point out the challenges faced by the transformation of immunoregulatory hydrogels into clinical products, and propose future research directions to promote its clinical application.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102870"},"PeriodicalIF":10.9,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144861328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nano TodayPub Date : 2025-08-15DOI: 10.1016/j.nantod.2025.102868
Yu Lu , Chang Liu , Qifan Zhou , Yan Huang , Jingwei Yi , Wei Jin , Zhonghua Liu , Bangshun He , Xiangwei Zhao
{"title":"Ultralow-cost personal PCRstrip with volumetric heating based on broadband absorption plasmonic fabric for POCT of pathogens","authors":"Yu Lu , Chang Liu , Qifan Zhou , Yan Huang , Jingwei Yi , Wei Jin , Zhonghua Liu , Bangshun He , Xiangwei Zhao","doi":"10.1016/j.nantod.2025.102868","DOIUrl":"10.1016/j.nantod.2025.102868","url":null,"abstract":"<div><div>The diagnosis of respiratory viral infection via reverse transcription-polymerase chain reaction (RT-PCR) is typically conducted in centralized laboratories using bulky equipment, and the procedure requires 1–2 h to complete. To prevent the spread of infectious diseases, there is an urgent need for ultrafast and accessible molecular diagnostic tools for point-of-care testing (POCT). Here, we developed an ultrafast, POC molecular diagnostic PCRstrip capable of detecting influenza A RNA with high sensitivity (1 copy/μL) in just 15 min. Our system integrated reverse transcription, rapid thermocycling and visual detection at ultralow cost. Broadband absorption plasmonic fabric (BAPF) with excellent photothermal effect was fabricated for volumetric photothermal heating excited by a cost-effective white LED. After photothermal PCR, amplification products can be visually detected by a lateral flow paper strip. Clinical validation of 80 nasopharyngeal swab samples collected from patients suspected of influenza A infection demonstrated a clinical sensitivity of 98.4 % and specificity of 100 %. This fast, ultralow-cost and reliable molecular diagnosis strategy is conducive to POCT, offering an effective tool for untrained personnel to detect and control infectious diseases individually.</div></div>","PeriodicalId":395,"journal":{"name":"Nano Today","volume":"65 ","pages":"Article 102868"},"PeriodicalIF":10.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}