A Tumor-Targeting Perovskite Quantum Dot with High Luminescence and Stability for Radiotherapy Sensitization through X-ray-Activated Photoelectrocatalysis

Abstract Radiotherapy (RT) remains a cornerstone in lung cancer management, yet its efficacy is often compromised by radiation resistance and off-target toxicity. Metal halide perovskites exhibit high potential for biomedical applications owing to their exceptional fluorescence imaging and photoelectric conversion capabilities, offering distinct radiosensitization advantages via high-Z elements and radiation-excited electron‒hole pairs. However, their poor physiological stability and limited biocompatibility have hindered biomedical translation. Herein, we construct an optimized multifunctional perovskite quantum dot (PQD) modified with chitosan-folate (CS-FA) (Cs-Sn-Pb-Br@CS-FA), which maintains long-term retention of photoluminescence and optical absorption properties in water for over 200 days, enabling specific tumor lesion tracing. Upon X-ray irradiation, the Cs-Sn-Pb-Br@CS-FA can promote the generation of multiple reactive oxygen species (ROS) through photoelectrocatalytically-induced electron‒hole pair separation and triplet energy transfer (TET). Moreover, the generated holes can simultaneously deplete endogenous glutathione (GSH), amplifying ROS accumulation and enhancing radiotherapeutic efficiency to promote tumor cell death. Biosafety assessment verified minimal toxicity to normal tissues at therapeutic doses, with intact fluorescent nanoparticles excreted via feces in their undecomposed perovskite form. In vivo study further underscored the dual functionality of the Cs-Sn-Pb-Br@CS-FA for precise tumor fluorescence imaging and effective radiosensitization in anti-tumor therapy. This work expands the biomedical application horizons of metal halide perovskites.