化学
肿瘤微环境
免疫原性细胞死亡
胰腺癌
活性氧
连接器
免疫疗法
癌细胞
单线态氧
癌症免疫疗法
生物物理学
癌症研究
免疫系统
癌症
生物化学
程序性细胞死亡
氧气
细胞凋亡
免疫学
肿瘤细胞
医学
生物
有机化学
内科学
计算机科学
操作系统
作者
Ningyue Yu,Jianhui Zhou,Mengbin Ding,M. Li,Shaojun Peng,Jingchao Li
标识
DOI:10.1002/anie.202405639
摘要
The high level of lactate in tumor microenvironment not only promotes tumor development and metastasis, but also induces immune escape, which often leads to failures of various tumor therapy strategies. We here report a sono‐triggered cascade lactate depletion strategy by using semiconducting polymer nanoreactors (SPNLCu) for cancer cuproptosis‐immunotherapy. The SPNLCu mainly contain a semiconducting polymer as sonosensitizer, lactate oxidase (LOx) conjugated via a reactive oxygen species (ROS)‐cleavable linker and chelated Cu2+. Upon ultrasound (US) irradiation, the semiconducting polymer generates singlet oxygen (1O2) to cut ROS‐cleavable linker to allow the release of LOx that catalyzes lactate depletion to produce hydrogen peroxide (H2O2). The Cu2+ will be reduced to Cu+ in tumor microenvironment, which reacts with the produced H2O2 to obtain hydroxyl radical (·OH) that further improves LOx release via destroying ROS‐cleavable linkers. As such, sono‐triggered cascade release of LOx achieves effective lactate depletion, thus relieving immunosuppressive roles of lactate. Moreover, the toxic Cu+ induces cuproptosis to cause immunogenic cell death (ICD) for activating antitumor immunological effect. SPNLCu are used to treat both subcutaneous and deep‐tissue orthotopic pancreatic cancer with observably enhanced efficacy in restricting the tumor growths. This study thus provides a precise and effective lactate depletion tactic for cancer therapy.
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