Journal
ADVANCED MATERIALS
Volume 33, Issue 49, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adma.202104037
Keywords
cancer immunotherapy; cGAS; STING; drug delivery; hepatocellular carcinoma; nanomedicine
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Funding
- National Natural Science Foundation of China [81827804, 81772546]
- Key Research and Development Project of Zhejiang Province [2018C03083, 2020C04005]
- China Postdoctoral Science Foundation [2021M692800]
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This study demonstrated that ZnS@BSA nanoclusters, synthesized through a self-assembly approach, significantly enhance cGAS/STING signals by releasing zinc ions in the acidic tumor microenvironment, leading to improved immunotherapy efficacy against hepatocellular carcinoma.
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.
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