Chiral iron single-atom nanozymes for enhanced photothermal chemodynamic cancer therapy

Chiral nanomaterials have great potential for enhancing clinical therapeutic efficacy, attributed to the distinctive chiral selectivity in biosystems. Herein, we designed chiral iron single-atom nanoenzymes (L/D-Cys@SAFe/NC) that exhibit remarkable tumor microenvironment-triggered catalytic therapeutic activity, by simultaneously depleting GSH and generating potent reactive oxygen species in cancer cells. Under laser irradiation, they displays photothermal-enhanced catalytic activities. The study of L/D-Cys@SAFe/NC on cancer cells shows that D-Cys@SAFe/NC exhibits stronger cytotoxicity than L-Cys@SAFe/NC due to the stronger internalization ability, also supported by the higher efficiency of cancer therapy of D-Cys@SAFe/NC in vivo. This research demonstrates that the chirality of the surface ligand of the nanomaterials could exert a substantial impact on their efficacy in treating cancer, which opens a novel way for the advancement of anticancer nanomedicine.