先天免疫系统
免疫系统
氧化磷酸化
肿瘤微环境
免疫
线粒体DNA
获得性免疫系统
癌症
细胞毒性T细胞
细胞生物学
DNA
免疫学
DNA损伤
线粒体
生物
癌症研究
基因
生物化学
体外
遗传学
作者
Han Jiang,Yuedong Guo,Chenyang Wei,Ping Hu,Jianlin Shi
标识
DOI:10.1002/adma.202008065
摘要
Abstract The innate immune system plays a key role in protecting the human body from tumors, which, unfortunately, is largely counteracted by their immune‐suppression function. Such an immune suppression has been reported to be induced by the immunosuppressive microenvironment, including the exhausted cytotoxic T lymphocytes (CTLs) and tumor‐promoting M2‐polarized macrophages. Here, a novel tumor‐immunotherapeutic modality based on the nanocatalytic innate immunity activation by tumor‐specific mitochondrial DNA (mtDNA) oxidative damage is proposed. In detail, a nanocatalytic medicine, Fe 2+ –Ru 2+ ‐loaded mesoporous silica nanoparticle named as MSN‐Ru 2+ /Fe 2+ (MRF), is constructed to induce oxidative damage in the mtDNA of tumor cells. Such an oxidative mtDNA is able to escape from the tumor cells and acts as an immunogenic damage‐associated molecular pattern to M1‐polarize tumor‐associated macrophages (TAMs), resulting in the reactivated immunoresponse of macrophages against cancer cells, and the subsequent inflammatory response of innate immunity. Most importantly, the treatment strategy based on regulating the innate immune response of TAMs not only stops the primary tumor progression, but also almost completely inhibits the growth of distant tumors in the periods of treatments.
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