An electrically activable nanochip to intensify gas-ionic-immunotherapy  

电激活ZnS纳米芯片用于增效肿瘤气体-离子-免疫治疗

作　　者：Gang Wang Jingrui Li Shumin Sun Yuqi Yang Zhihui Han Zifan Pei Liang Cheng 王刚;李璟睿;孙淑敏;杨雨琦;韩智慧;裴梓帆;程亮

机构地区：[1]Institute of Functional Nano&Soft Materials(FUNSOM),Jiangsu Key Laboratory for Carbon-Based Functional Materials&Devices,Soochow University,Suzhou 215123,China

出　　处：《Science Bulletin》2025年第3期390-406,共17页科学通报(英文版)

基　　金：supported by the National Research Programs of China(2022YFB3804600);the National Natural Science Foundation of China(52472288,U20A20254,and 52072253);Collaborative Innovation Center of Suzhou Nano Science and Technology,Suzhou Key Laboratory of Nanotechnology and Biomedicine,Jiangsu Natural Science Fund for Distinguished Young Scholars(BK20211544);111 Project,and Joint International Research Laboratory of Carbon-Based Functional Materials and Devices,Science and Technology Development Fund Macao SAR(0118/2023/RIA2,0064/2024/AMJ,and 0016/2024/RIA1);Natural Science Foundation of Shandong Province(ZR2021QH315);Suzhou Key Laboratory of Nanotechnology and Biomedicine,and Key Laboratory of Structural Deformities in Children of Suzhou(Szs2022018).

摘　　要：Excess intracellular H_(2)S induces destructive mitochondrial toxicity,while overload of Zn^(2+)results in cell pyroptosis and potentiates the tumor immunogenicity for immunotherapy.However,the precise delivery of both therapeutics remains a great challenge.Herein,an electrically activable ZnS nanochip for the controlled release of H_(2)S and Zn^(2+)was developed for enhanced gas-ionic-immunotherapy(GIIT).Under an electric field,a locality with particularly high concentrations of H_(2)S and Zn^(2+)was established by the voltage-controlled degradation of the ZnS nanoparticles(NPs).Consequently,the ZnS nanochip-mediated gas-ionic therapy(GIT)resulted in mitochondrial membrane potential depolarization,energy generation inhibition,and oxidative stress imbalance in tumor cells.Interestingly,the cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes(cGAS-STING)signaling pathway was activated due to the mitochondrial destruction.Moreover,the released Zn^(2+)resulted in the increase of the intracellular Zn levels and cell pyroptosis,which enhanced the immunogenicity via the release of damage-associated molecular patterns(DAMPs).In vitro and in vivo studies revealed that the ZnS nanochip-based GIT effectively eliminated the tumors under an electric field and mobilized the cytotoxic T lymphocytes for immunotherapy.The combination withαCTLA-4 further promoted the adaptive immune response and inhibited tumor metastasis and long-term tumor recurrence.This work presented an electrically activable ZnS nanochip for combined immunotherapy,which might inspire the development of electric stimulation therapy.

关 键 词：H_(2)S gas therapy lonic interference therapy Electrically controll eddelivery Cell pyroptosis CGAS-STING pathway 

分 类 号：R73[医药卫生—肿瘤]