Atomic‐Precision Symmetry Breaking in Bi‐O‐Ti Sites Enables ROS Generation for Bactericidal and Osteosarcoma Therapy

ABSTRACT Photocatalytic therapy, which generates reactive oxygen species (ROS) upon light irradiation, has garnered significant interest for antibacterial and anticancer applications. This study establishes a doping‐engineered photocatalytic platform for antibacterial activity and precision osteosarcoma therapy by atomically constructing asymmetric Bi‐O‐Ti active sites within mesoporous TiO 2 nanospheres. Strategic Bi doping disrupts crystallographic symmetry while preserving structural integrity, enabling tripartite optimization of geometric configurations, electronic states, and coordination environments. The mesoporous architecture provides a high surface area (126.5 m 2 g −1 ), exposing abundant accessible Bi‐O‐Ti active sites. Engineered Bi doping enhances charge mobility and preserves redox capacity. Density functional theory (DFT) calculations and femtosecond transient absorption spectroscopy confirm the dual functionality of Bi‐O‐Ti moieties. Bi doping introduces mid‐gap defect states that act as electron‐trapping centers, enabling ultrafast (< 10 ps) electron transfer from the conduction band and suppressing recombination, whereas Bi‐O‐Ti sites serve as active adsorption centers, enhancing O 2 and H 2 O adsorption (−4.72 eV) and facilitating ROS generation. Benefiting from amplified ROS production, Bi‐TiO 2 demonstrates potent bactericidal efficacy against both Gram‐positive Staphylococcus aureus ( S. aureus ; 99.9% inactivation within 60 min) and Gram‐negative Escherichia coli ( E. coli ; 48.9% efficiency at 90 min). Furthermore, Bi‐TiO 2 nanospheres exhibit biocompatibility in cellular assays. Notably, under light irradiation, they display superior antiproliferative and antimigratory effects against osteosarcoma cells compared to pure TiO 2 , achieving a 10.5‐fold reduction in IC 50 values, alongside enhanced intracellular ROS generation. This work pioneers a crystallographic symmetry‐breaking strategy that orchestrates electronic structure modulation and ROS management for effective PDT.