癌症研究
二硫仑
免疫原性细胞死亡
药理学
细胞凋亡
免疫疗法
化学
程序性细胞死亡
材料科学
生物
生物化学
免疫学
免疫系统
作者
Ting Li,Ying Zhang,Jie Zhu,Fangrui Zhang,Anan Xu,Tian Zhou,Yaoqi Li,Ming Liu,Hengte Ke,Tao Yang,Yongan Tang,Jing Tao,Liyan Miao,Yibin Deng,Huabing Chen
标识
DOI:10.1002/adma.202210201
摘要
Artificial enzymes have demonstrated therapeutic benefits against diverse malignant tumors, yet their antitumor potencies are still severely compromised by non-selective catalysis, low atomic-utilization efficiency, and undesired off-target toxicity. Herein, it is reported that peroxidase-like biomineralized copper (II) carbonate hydroxide nanocrystals inside single albumin nanocages (CuCH-NCs) act as a pH-activatable proenzyme to achieve tumor-selective and synergistic chemodynamic/chemo-immunotherapy against aggressive triple-negative breast cancers (TNBCs). These CuCH-NCs show pH-sensitive Cu2+ release, which spontaneously undergoes glutathione (GSH)-mediated reduction into Cu+ species for catalyzing the evolution of H2 O2 into hydroxyl radicals (·OH) in a single-atom-like manner to cause chemodynamic cell injury, and simultaneously activates non-toxic disulfiram to cytotoxic complex for yielding selective chemotherapeutic damage via blocking cell proliferation and amplifying cell apoptosis. CuCH-NCs exhibit considerable tumor-targeting capacity with deep penetration depth, thus affording preferable efficacy against orthotopic breast tumors through synergistic chemodynamic/chemotherapy, together with good in vivo safety. Moreover, CuCH-NCs arouse distinct immunogenic cell death effect and upregulate PD-L1 expression upon disulfiram combination, and thus synergize with anti-PD-L1 antibody to activate adaptive and innate immunities, together with relieving immunosuppression, finally yielding potent antitumor efficacy against both primary and metastatic TNBCs. These results provide insights into smart and high-performance proenzymes for synergistic therapy against aggressive cancers.
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