{"title":"x射线响应半导体聚合物siRNA纳米系统通过沉默免疫抑制信号治疗原位胶质瘤","authors":"Meng Li, Yiduo Zhan, Zichao Li, Wenzhi Tu*, Ting Su*, Yong Liu* and Jingchao Li*, ","doi":"10.1021/acsnano.4c1189210.1021/acsnano.4c11892","DOIUrl":null,"url":null,"abstract":"<p >Gliomas are the most lethal types of adult brain tumors with a devastating prognosis, but many therapies have failed to exert good therapeutic benefits because of the extremely hypoxic and immunosuppressive tumor microenvironment. To address these challenges, we herein present a semiconducting polymer (SP)-based small interfering RNA (siRNA) nanosystem with the loading of oxygen self-supplying perfluorohexane (PFH) and conjugation of siRNA via a singlet oxygen (<sup>1</sup>O<sub>2</sub>)-cleavable linker. The nanosystems are further camouflaged with a macrophage membrane to obtain the final RM@SPN-siRNA. RM@SPN-siRNA displays an enhanced enrichment at the orthotopic glioma site due to surface cell membrane camouflaging. PFH provides sufficient oxygen to relieve tumor hypoxia, which boosts the production of <sup>1</sup>O<sub>2</sub> by the SP working as the radiosensitizer under external X-ray irradiation. The generated <sup>1</sup>O<sub>2</sub> destroys the <sup>1</sup>O<sub>2</sub>-cleavable linker and disrupts the membrane structure to enable in situ siRNA release at the tumor site and subsequent activatable programmed death ligand-1 (PD-L1) silencing for tumor cells. As a consequence, an immunological effect is triggered to effectively inhibit tumor growths in an orthotopic glioma mouse model. This study offers an X-ray-responsive siRNA nanosystem for precise protein silencing and treatment of deep-seated orthotopic tumors.</p>","PeriodicalId":21,"journal":{"name":"ACS Nano","volume":"19 18","pages":"17247–17260 17247–17260"},"PeriodicalIF":16.0000,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"X-ray-Responsive Semiconducting Polymer siRNA Nanosystems for Orthotopic Glioma Treatment via Silencing the Immunosuppressive Signal\",\"authors\":\"Meng Li, Yiduo Zhan, Zichao Li, Wenzhi Tu*, Ting Su*, Yong Liu* and Jingchao Li*, \",\"doi\":\"10.1021/acsnano.4c1189210.1021/acsnano.4c11892\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Gliomas are the most lethal types of adult brain tumors with a devastating prognosis, but many therapies have failed to exert good therapeutic benefits because of the extremely hypoxic and immunosuppressive tumor microenvironment. To address these challenges, we herein present a semiconducting polymer (SP)-based small interfering RNA (siRNA) nanosystem with the loading of oxygen self-supplying perfluorohexane (PFH) and conjugation of siRNA via a singlet oxygen (<sup>1</sup>O<sub>2</sub>)-cleavable linker. The nanosystems are further camouflaged with a macrophage membrane to obtain the final RM@SPN-siRNA. RM@SPN-siRNA displays an enhanced enrichment at the orthotopic glioma site due to surface cell membrane camouflaging. PFH provides sufficient oxygen to relieve tumor hypoxia, which boosts the production of <sup>1</sup>O<sub>2</sub> by the SP working as the radiosensitizer under external X-ray irradiation. The generated <sup>1</sup>O<sub>2</sub> destroys the <sup>1</sup>O<sub>2</sub>-cleavable linker and disrupts the membrane structure to enable in situ siRNA release at the tumor site and subsequent activatable programmed death ligand-1 (PD-L1) silencing for tumor cells. As a consequence, an immunological effect is triggered to effectively inhibit tumor growths in an orthotopic glioma mouse model. This study offers an X-ray-responsive siRNA nanosystem for precise protein silencing and treatment of deep-seated orthotopic tumors.</p>\",\"PeriodicalId\":21,\"journal\":{\"name\":\"ACS Nano\",\"volume\":\"19 18\",\"pages\":\"17247–17260 17247–17260\"},\"PeriodicalIF\":16.0000,\"publicationDate\":\"2025-05-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Nano\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acsnano.4c11892\",\"RegionNum\":1,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Nano","FirstCategoryId":"88","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsnano.4c11892","RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
X-ray-Responsive Semiconducting Polymer siRNA Nanosystems for Orthotopic Glioma Treatment via Silencing the Immunosuppressive Signal
Gliomas are the most lethal types of adult brain tumors with a devastating prognosis, but many therapies have failed to exert good therapeutic benefits because of the extremely hypoxic and immunosuppressive tumor microenvironment. To address these challenges, we herein present a semiconducting polymer (SP)-based small interfering RNA (siRNA) nanosystem with the loading of oxygen self-supplying perfluorohexane (PFH) and conjugation of siRNA via a singlet oxygen (1O2)-cleavable linker. The nanosystems are further camouflaged with a macrophage membrane to obtain the final RM@SPN-siRNA. RM@SPN-siRNA displays an enhanced enrichment at the orthotopic glioma site due to surface cell membrane camouflaging. PFH provides sufficient oxygen to relieve tumor hypoxia, which boosts the production of 1O2 by the SP working as the radiosensitizer under external X-ray irradiation. The generated 1O2 destroys the 1O2-cleavable linker and disrupts the membrane structure to enable in situ siRNA release at the tumor site and subsequent activatable programmed death ligand-1 (PD-L1) silencing for tumor cells. As a consequence, an immunological effect is triggered to effectively inhibit tumor growths in an orthotopic glioma mouse model. This study offers an X-ray-responsive siRNA nanosystem for precise protein silencing and treatment of deep-seated orthotopic tumors.
期刊介绍：
ACS Nano, published monthly, serves as an international forum for comprehensive articles on nanoscience and nanotechnology research at the intersections of chemistry, biology, materials science, physics, and engineering. The journal fosters communication among scientists in these communities, facilitating collaboration, new research opportunities, and advancements through discoveries. ACS Nano covers synthesis, assembly, characterization, theory, and simulation of nanostructures, nanobiotechnology, nanofabrication, methods and tools for nanoscience and nanotechnology, and self- and directed-assembly. Alongside original research articles, it offers thorough reviews, perspectives on cutting-edge research, and discussions envisioning the future of nanoscience and nanotechnology.
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