ZnS@BSA Nanoclusters Potentiate Efficacy of Cancer Immunotherapy
ZnS@BSA Nanoclusters Potentiate Efficacy of Cancer Immunotherapy
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DOI：
10.1002/adma.202104037
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发表时间：
2021-10-07
影响因子：
29.4
通讯作者：
Cai, Xiujun
中科院分区：
文献类型：
--
作者：
Cen, Dong;Ge, Qiwei;Cai, Xiujun
虽然免疫检查点抑制剂等免疫疗法在癌症治疗中显示出良好的疗效，但患者的反应相对有限。激活环状鸟苷-一磷酸腺苷合成酶/干扰素基因刺激物(cGAS/STIN)信号通路以上调天然免疫已成为加强肿瘤免疫治疗的新策略。本文报道了用自组装方法合成的锌离子纳米簇，其中酸性肿瘤微环境下释放的锌离子显著增强了cGAS/STAR信号。同时，细胞内的锌离子可以产生活性氧物种，而通过特异性地抑制肝癌细胞中的过氧化氢酶，细胞内锌离子产生的硫化氢气体进一步促进了这一过程。研究发现，纳米簇激活了小鼠体内的cGAS/STIN信号，促进了CD8(+)T细胞在肿瘤部位的渗透和树突状细胞的交叉呈递，从而提高了对肝癌的免疫治疗效果。
Although immunotherapy such as immune checkpoint inhibitors has shown promising efficacy in cancer treatment, the responsiveness among patients is relatively limited. Activation of the cyclic guanosine monophosphate-adenosine monophosphate synthase/interferon gene stimulator (cGAS/STING) signaling pathway to upregulate innate immunity has become an emerging strategy for enhancing tumor immunotherapy. Herein, ZnS@BSA (bovine serum albumin) nanoclusters synthesized via a self-assembly approach are reported, where the released zinc ions under acidic tumor microenvironment significantly enhance cGAS/STING signals. Meanwhile, intracellular zinc ions can produce reactive oxygen species, which is further facilitated by the generated H2S gas from ZnS@BSA via specifically inhibiting catalase in hepatocellular carcinoma cells. It is found that the nanoclusters activate the cGAS/STING signals in mice, which promotes the infiltration of CD8(+) T cells at the tumor site and cross-presentation of dendritic cells, leading to an improved immunotherapy efficacy against hepatocellular carcinoma.