Boosting H2O2-Guided Chemodynamic Therapy of Cancer by Enhancing Reaction Kinetics through Versatile Biomimetic Fenton Nanocatalysts and the Second Near-Infrared Light Irradiation

Fenton reaction-based chemodynamic therapy (CDT) has attracted considerable attention for tumor treatment, because the Fenton reaction can degrade endogenous H2O2 within the tumor to form reactive oxygen species (ROS) to kill cancer cells. The kinetics of the Fenton reaction has significantly influenced its treatment efficacy. It is crucial to enhance the reaction kinetics at the maximum H2O2 concentration to quickly produce vast amounts of ROS to achieve treatment efficacy, which to date, has not been realized. Herein, reported is an efficacious CDT treatment of breast cancer using biomimetic CS-GOD@CM nanocatalysts, which are rationally designed to significantly boost the Fenton reaction through improvement of H2O2 concentration within tumors, and application of the second near-infrared (NIR-II) light irradiation at the maximum concentration, which is monitored by photoacoustic imaging. The biomimetic nanocatalysts are composed of ultra-small Cu2-xSe (CS) nanoparticles, glucose oxidase (GOD), and tumor cell membrane (CM). The nanocatalysts can be retained in tumor for more than two days to oxidize glucose and produce an approximately 2.6-fold increase in H2O2 to enhance the Fenton reaction under the NIR-II irradiation. This work demonstrates for the first time the CDT treatment of cancer enhanced by the NIR-II light.