Cascade Radical Storm Triggered by Adaptive AIE Photosensitizer for Hypoxia Alleviation and Enhanced Photodynamic Therapy of Drug‐Resistant Bacteria

ABSTRACT Traditional type I photodynamic therapy (PDT) is limited in treating bacterial infections because hypoxic conditions at the lesion site and the barrier effect of the high‐viscosity extracellular polymeric matrix within biofilms significantly reduce its antibacterial efficacy. To address this challenge, we propose an adaptive aggregation‐induced emission (AIE) photosensitizer, DTPy‐Bio, based on a synergistic cation‐biotin molecular engineering strategy. This photosensitizer not only exhibits outstanding photoinduced intermolecular electron transfer and charge separation, enabling efficient generation of reactive oxygen species (ROS) under illumination, but its aggregates also demonstrate excellent semiconductor‐like behavior. This allows it to generate oxygen in situ via water oxidation under hypoxic conditions and further triggers a cascade of electron transfer to form a radical storm that achieves highly efficient killing of drug‐resistant bacteria. Notably, DTPy‐Bio exhibits significant viscosity‐responsive properties, and its photosensitization activity is further enhanced in high‐viscosity biofilm microenvironments, demonstrating excellent microenvironmental adaptability. The experimental results showed that DTPy‐Bio achieved an antibacterial rate of 94.46% against methicillin‐resistant Staphylococcus aureus ( MRSA ) and promoted exceptional wound healing in infected wound models. This study provides an innovative approach for developing novel, highly efficient type I photosensitizers with microenvironmental adaptability, offering a new strategy to overcome treatment challenges associated with bacterial biofilms.