Bismuth Sulfide Nanorods with Retractable Zinc Protoporphyrin Molecules for Suppressing Innate Antioxidant Defense System and Strengthening Phototherapeutic Effects

Abstract Bismuth (Bi)‐based nanomaterials (NMs) are widely used for computed tomography (CT) imaging guided photothermal therapy, however, the photodynamic property is hardly exhibited by these NMs due to the fast electron–hole recombination within their narrow bandgap. Herein, a sophisticated nanosystem is designed to endow bismuth sulfide (Bi₂S₃) nanorods (NRs) with potent photodynamic property. Zinc protoporphyrin IX (ZP) is linked to Bi₂S₃ NRs through a thermoresponsive polymer to form BPZP nanosystems. The stretching ZP could prebind to the active site of heme oxygenase‐1 overexpressed in cancer cells, suppressing the cellular antioxidant defense capability. Upon NIR laser irradiation, the heat released from Bi₂S₃ NRs could retract the polymer and drive ZP to the proximity of Bi₂S₃ NRs, facilitating an efficient electron–hole separation in ZP and Bi₂S₃ NRs, and leading to reactive oxygen species generation. In vitro and in vivo studies demonstrate the promising photodynamic property of BPZP, together with their photothermal and CT imaging performance.