Photo/chemo dynamic insights into the modulation of CuSe _<i>x</i> via Fe dopant for enhanced synergistic therapy

Abstract Nanodynamic therapy integrating the merits of different dynamic therapy for maximizing the reactive oxygen species (ROS) generation serves as a highly efficient anti‐tumor strategy. Gaining dynamic insights into how nanomaterials modulate the anti‐tumor performance guides the rational design of nano‐drugs. Herein, over biocompatible CuSe x nanoparticles which have been applied in photothermal therapy, Fe species are doped for modulating the absorption profiles for ROS and bandgap of CuSe x , finally regulating the chemodynamic (CDT) and photodynamic (PDT) therapeutic performance. Experimental evidence demonstrates that Fe doped materials (FCS) endow the CuSe x with enhanced photothermal efficiency, thus thermodynamically promotes the temperature‐dependent peroxidase (POD)‐like and oxidase (OXD)‐like catalytic performance for transforming the abundant endogenous H 2 O 2 into more highly toxic ROS. In addition, the dopant of Fe species decreases the bandgap of CuSe x from 1.45 to 1.30 eV, suggesting that the PDT could be realized over FCS under the irradiation of redshifted NIR light, which is more clinically favorable. In vitro and in vivo experiments manifests that that FCS overtakes CuSe x by effectively generating ROS storms under NIR light while depleting overexpressed GSH, inducing tumor cell death through dual pathways. This work offers a novel perspective for the design of smart‐responsive nanomedicine.