传出细胞增多
刺
癌症免疫疗法
川地163
癌症研究
免疫疗法
药理学
医学
生物
材料科学
癌症
巨噬细胞
内科学
生物化学
体外
工程类
航空航天工程
作者
Zhiyan Li,Xianghui Li,Yanjun Lu,Xudong Zhu,Wenxuan Zheng,Kai Chen,Xingzhou Wang,Tao Wang,Wenxian Guan,Zhi Su,Song Liu,Jinhui Wu
标识
DOI:10.1002/adma.202410937
摘要
Abstract Immunotherapy has emerged as a highly effective therapeutic strategy for cancer treatment. Cyclic guanosine monophosphate‐adenosine monophosphate synthase (cGAS)‐stimulator of interferon gene (STING) pathway activation facilitates tumor‐associated macrophage (TAM) polarization toward M1 phenotype, and Mn 2+ are effective agents for this pathway activation. However, the high in vivo degradation rate and toxicity of Mn 2+ hamper clinical application of immunotherapy. Here, this work has newly synthesized and screened manganese porphyrins for Mn 2+ transport, referred to as photo‐STING agonists (PSAs), and further encapsulate them into core‐shell nanoparticles named Rm@PP‐GA with dual specificity for tumor tissue and TAMs. Not only do PSAs achieve higher Mn 2+ delivery efficiency compared to Mn 2+ , but they also generate reactive oxygen species under light exposure, promoting mitochondrial DNA release for cGAS‐STING pathway activation. In Rm@PP‐GA, globin and red blood cell membranes (Rm) are used for erythrocyte efferocytosis‐mimicking delivery. Rm can effectively prolong the in vivo circulation period while globin enables PSAs to be taken up by TAMs via CD163 receptors. After Rm rupture mediated by perfluorohexane in nanoparticles under ultrasonication, drugs are specifically released for TAM repolarization. Further, dendritic cells mature, as well as T lymphocyte infiltrate, both of which favor tumor eradication. Therefore, cancer immunotherapy is optimized by novel PSAs delivered by erythrocyte efferocytosis‐mimicking delivery pattern.
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