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Zinc–Nickel Bimetallic Hydroxide Nanosheets Activate the Paraptosis–Pyroptosis Positive Feedback Cycle for Enhanced Tumor Immunotherapy

ACS Nano. 2024-10; 
Youdong Chen 1, Yujie Lu , Huali Lei 1, Lin Liu , Xianmin Li 1, Yuqi Yang 1, Shumin Sun 1, Qiao Yu 1, Li Wang 1, Jie Wu 1 2, Jingrui Li 1, Guanghui Hou 1, Liang Cheng
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Proteins, Expression, Isolation and Analysis An annexin V-FITC/PI apoptosisdetection kit was purchased from Meilunbio (Dalian, China). PrecastGels was purchased from GenScript Biotech Corporation. Get A Quote

Abstract

Immunotherapy holds significant promise for cancer treatment. However, the highly immunosuppressive nature of solid tumors limits its effectiveness. Herein, we developed bioactive zinc-nickel hydroxide (ZnNi(OH)4) nanosheets (NSs) that can effectively initiate the paraptosis-pyroptosis positive feedback cycle through synergistic ionic effect, thereby mitigating the immunosuppression of solid tumors and enhancing the efficacy of immunotherapy. The acid-sensitive ZnNi(OH)4 NSs releases Ni2+ and Zn2+ in the weakly acidic tumor microenvironment. The released Ni2+ alleviated pyroptosis inhibition by inducing paraptosis and inhibiting autophagic flux. Concurrently, Ni2+ triggered release of endogenous Zn2+ within the... More

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