Photothermo‐Promoted Nanocatalysis Combined with H2S‐Mediated Respiration Inhibition for Efficient Cancer Therapy

Nanocatalytic medicine has emerged as a promising method for the specific cancer therapy by mediating the interaction between tumor microenvironment biomarkers and nanoagents. However, the produced antitumor cell killing molecules, such as reactive oxygen species (ROS), by catalysis are insufficient to inhibit tumor growth. Herein, a novel kind of polyvinyl pyrrolidone modified multifunctional iron sulfide nanoparticles (Fe1−xS‐PVP NPs) is developed via a one‐step hydrothermal method, which exhibits high photothermal (PT) conversion efficiency (η = 24%) under the irradiation of 808 nm near‐infrared laser. The increased temperature further facilitates the Fenton reaction to generate abundant •OH radicals. More importantly, under an acidic (pH = 6.5) condition within tumor environment, the Fe1−xS‐PVP NPs can in situ produce H2S gas, which is evidenced to suppress the activity of enzyme cytochrome c oxidase (COX IV) in cancer cells, contributing to inhibit the growth of tumor. Both in vitro and in vivo results demonstrate that the H2S‐mediated gas therapy in combination with PT enhanced ROS achieves excellent antitumor performance, which can open up a new approach for the design of gas‐mediated cancer treatment. Based on nanocatalytic medicine, a novel strategy to combine H2S‐mediated gas therapy with photothermal enhanced reactive oxygen species via a facile but multifunctional nanoagent (Fe1−xS‐PVP NPs) is developed to achieve excellent antitumor performance. Additionally, H2S‐mediated gas therapy is beneficial to suppress the activity of enzyme cytochrome c oxidase and further inhibit cellular aerobic respiration and the decreased production of ATP.