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

Abstract 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 (Fe 1− x S‐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 Fe 1− x S‐PVP NPs can in situ produce H 2 S 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 H 2 S‐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.