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Mitochondrial rewiring with small-molecule drug-free nanoassemblies unleashes anticancer immunity

Nature Communications. 2024-09; 
Lulu Ren , Jianqin Wan , Xiaoyan Li , Jie Yao , Yan Ma , Fanchao Meng , Shusen Zheng , Weidong Han , Hangxiang Wang
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摘要

The immunosuppressive tumor microenvironment (TME) remains a major obstacle to tumor control and causes suboptimal responses to immune checkpoint blockade (ICB) therapy. Thus, developing feasible therapeutic strategies that trigger inflammatory responses in the TME could improve the ICB efficacy. Mitochondria play an essential role in inflammation regulation and tumor immunogenicity induction. Herein, we report the discovery and characterization of a class of small molecules that can recapitulate aqueous self-assembly behavior, specifically target cellular organelles (e.g., mitochondria), and invigorate tumor cell immunogenicity. Mechanistically, this nanoassembly platform dynamically rewires mitochondria, indu... More

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