Hydrogen sulfide(H2S)is the most recently discovered gasotransmitter molecule that activates multiple intracellular signaling pathways and exerts concentration-dependent antitumor effect by interfering with mitochondrial respiration and inhibiting cellular ATP generation.Inspired by the fact that H2S can also serve as a promoter for intracellular Ca2+influx,tumor-specific nanomodulators(I-CaS@PP)have been constructed by encapsulating calcium sulfide(CaS)and indocyanine green(ICG)into methoxy poly(ethylene glycol)-b-poly(lactide-co-glycolide)(PLGA-PEG).I-CaS@PP can achieve tumor-specific biodegradability with high biocompatibility and pH-responsive H2S release.The released H2S can effectively suppress the catalase(CAT)activity and synergize with released Ca2+to facilitate abnormal Ca2+retention in cells,thus leading to mitochondria destruction and amplification of oxidative stress.Mitochondrial dysfunction further contributes to blocking ATP synthesis and downregulating heat shock proteins(HSPs)expression,which is beneficial to overcome the heat endurance of tumor cells and strengthen ICG-induced photothermal performance.Such a H2S-boosted Ca2+-involved tumor-specific therapy exhibits highly effective tumor inhibition effect with almost complete elimination within 14-day treatment,indicating the great prospect of CaS-based nanomodulators as antitumor therapeutics.

Chuchu Lin;Chenyi Huang;Zhaoqing Shi;Meitong Ou;Shengjie Sun;Mian Yu;Ting Chen;Yunfei Yi;Xiaoyuan Ji;Feng Lv;Meiying Wu;Lin Mei

School of Pharmaceutical Sciences(Shenzhen),Shenzhen Campus of Sun Yat-sen University,Shenzhen 518107,China;Tianjin Key Laboratory of Biomedical Materials,Key Laboratory of Biomaterials and Nanotechnology for Cancer Immunotherapy,Institute of Biomedical Engineering,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin 300192,China;Academy of Medical Engineering and Translational Medicine,Medical College,Tianjin University,Tianjin 300072,China

药学学报（英文版）

[1]Chuchu Lin;Chenyi Huang;Zhaoqing Shi;Meitong Ou;Shengjie Sun;Mian Yu;Ting Chen;Yunfei Yi;Xiaoyuan Ji;Feng Lv;Meiying Wu;Lin Mei-.Biodegradable calcium sulfide-based nanomodulators for H2S-boosted Ca2+-involved synergistic cascade cancer therapy)[J].药学学报（英文版）,2022(12):4472-4485

nanomodulators,gasotransmitter,glycolide,Ca2+to,Ca2+retention

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