{"title":"半导体电荷反转纳米抗氧化剂的免疫调节工程,用于改善癌症放射免疫otheranostics。","authors":"Wen Ma, Haifen Luo, Jingqi Lv, Peiye Wen, Gang Liu, Zhiqiang Yu, Zhen Yang, Wei Huang","doi":"10.1002/adma.202402929","DOIUrl":null,"url":null,"abstract":"<p>Radiotherapy (RT) is a crucial clinical modality for cancer. However, nonselectivity, toxicity to normal tissues, and radio-resistance severely limit RT applications. This study develops a versatile X-ray theranostic nano-antioxidant (XTN) to prevent normal tissues from oxidative damage and induce systematic and robust anticancer immunity. XTN owns NIR-II photoacoustic (PA) imaging properties for precise discrimination of the tumor margin through, thereby improving the accuracy of RT. Additionally, XTN is a nano-antioxidant to enhance the cell viability of normal cells after irradiation. Most importantly, XTN scavenges reactive oxygen species (ROS) in the TME to preserve the stimulatory activity of released high mobility group protein B1 to dendritic cells (DCs) and recover T cells’ immune function. Meanwhile, XTN achieves charge-reversal specifically releasing an immunomodulator (demethylcantharidin, DMC) in the acidic TME. Moreover, the specifically released DMC inhibits protein phosphatase-2A activity and reduces regulatory T cell (Treg) differentiation. In the bilateral 4T1 tumor model, XTN-mediated radioimmunotherapy remarkably boosts a systemic antitumor immune response and induces durable immunological memory against tumor growth.</p>","PeriodicalId":114,"journal":{"name":"Advanced Materials","volume":null,"pages":null},"PeriodicalIF":27.4000,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Immunoregulatory Engineering of Semiconducting Charge-Reversal Nanoantioxidant for Ameliorating Cancer Radioimmunotheranostics\",\"authors\":\"Wen Ma, Haifen Luo, Jingqi Lv, Peiye Wen, Gang Liu, Zhiqiang Yu, Zhen Yang, Wei Huang\",\"doi\":\"10.1002/adma.202402929\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>Radiotherapy (RT) is a crucial clinical modality for cancer. However, nonselectivity, toxicity to normal tissues, and radio-resistance severely limit RT applications. This study develops a versatile X-ray theranostic nano-antioxidant (XTN) to prevent normal tissues from oxidative damage and induce systematic and robust anticancer immunity. XTN owns NIR-II photoacoustic (PA) imaging properties for precise discrimination of the tumor margin through, thereby improving the accuracy of RT. Additionally, XTN is a nano-antioxidant to enhance the cell viability of normal cells after irradiation. Most importantly, XTN scavenges reactive oxygen species (ROS) in the TME to preserve the stimulatory activity of released high mobility group protein B1 to dendritic cells (DCs) and recover T cells’ immune function. Meanwhile, XTN achieves charge-reversal specifically releasing an immunomodulator (demethylcantharidin, DMC) in the acidic TME. Moreover, the specifically released DMC inhibits protein phosphatase-2A activity and reduces regulatory T cell (Treg) differentiation. In the bilateral 4T1 tumor model, XTN-mediated radioimmunotherapy remarkably boosts a systemic antitumor immune response and induces durable immunological memory against tumor growth.</p>\",\"PeriodicalId\":114,\"journal\":{\"name\":\"Advanced Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":27.4000,\"publicationDate\":\"2024-06-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advanced Materials\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/adma.202402929\",\"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":"Advanced Materials","FirstCategoryId":"88","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/adma.202402929","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}
引用次数: 0
摘要
放射治疗(RT)是治疗癌症的重要临床方式。然而,非选择性、对正常组织的毒性和放射抗性严重限制了 RT 的应用。在这项研究中,我们开发了一种多功能的 X 射线治疗纳米抗氧化剂(XTN),以防止正常组织受到氧化损伤,并诱导系统而强大的抗癌免疫。XTN 具有近红外-II 光声成像特性,可精确分辨肿瘤边缘,从而提高 RT 的准确性。此外,XTN 还是一种纳米抗氧化剂,可提高正常细胞在辐照后的存活率。最重要的是,XTN 能清除 TME 中的 ROS,保持释放的高迁移率基团蛋白 B1 对树突状细胞的刺激活性,恢复 T 细胞的免疫功能。同时,XTN 还能在酸性 TME 中特异性释放一种免疫调节剂(去甲基桔梗素,DMC),从而实现电荷反转。此外,特异性释放的 DMC 还能抑制蛋白磷酸酶-2A 的活性,减少调节性 T 细胞的分化。在双侧4T1肿瘤模型中,XTN介导的放射免疫疗法显著增强了全身抗肿瘤免疫反应,并诱导了针对肿瘤生长的持久免疫记忆。本文受版权保护。保留所有权利。
Immunoregulatory Engineering of Semiconducting Charge-Reversal Nanoantioxidant for Ameliorating Cancer Radioimmunotheranostics
Radiotherapy (RT) is a crucial clinical modality for cancer. However, nonselectivity, toxicity to normal tissues, and radio-resistance severely limit RT applications. This study develops a versatile X-ray theranostic nano-antioxidant (XTN) to prevent normal tissues from oxidative damage and induce systematic and robust anticancer immunity. XTN owns NIR-II photoacoustic (PA) imaging properties for precise discrimination of the tumor margin through, thereby improving the accuracy of RT. Additionally, XTN is a nano-antioxidant to enhance the cell viability of normal cells after irradiation. Most importantly, XTN scavenges reactive oxygen species (ROS) in the TME to preserve the stimulatory activity of released high mobility group protein B1 to dendritic cells (DCs) and recover T cells’ immune function. Meanwhile, XTN achieves charge-reversal specifically releasing an immunomodulator (demethylcantharidin, DMC) in the acidic TME. Moreover, the specifically released DMC inhibits protein phosphatase-2A activity and reduces regulatory T cell (Treg) differentiation. In the bilateral 4T1 tumor model, XTN-mediated radioimmunotherapy remarkably boosts a systemic antitumor immune response and induces durable immunological memory against tumor growth.
期刊介绍:
Advanced Materials, one of the world's most prestigious journals and the foundation of the Advanced portfolio, is the home of choice for best-in-class materials science for more than 30 years. Following this fast-growing and interdisciplinary field, we are considering and publishing the most important discoveries on any and all materials from materials scientists, chemists, physicists, engineers as well as health and life scientists and bringing you the latest results and trends in modern materials-related research every week.