pH-Responsive AIE Photosensitizers for Enhanced Antibacterial Therapy

Abstract

Bacterial infections significantly alter the local microenvironment, with acidic byproducts from bacterial metabolism leading to a pronounced pH reduction. Leveraging this characteristic, we synthesized and identified DHTPA, a near-infrared (NIR) fluorescent and pH-responsive aggregation-induced emission (AIE) photosensitizer, for enhanced photodynamic therapy against bacterial infections. DHTPA aggregates exhibit a 2.1-fold increase in ROS generation under weakly acidic conditions (pH 5.5) compared to neutral conditions (pH 7.4), attributed to its pH-dependent electronic structure modulation. Upon NIR light irradiation, DHTPA aggregates precisely respond to the acidic microenvironment, significantly boosting ROS production for efficient bacterial eradication. In vitro studies demonstrated that DHTPA achieved over 99.9% bactericidal efficiency against both gram-negative and gram-positive bacteria. In a murine infected wound model, DHTPA treatment accelerated wound healing by 2.4 times, markedly reduced bacterial burden, and alleviated inflammatory responses, highlighting its therapeutic potential. By integrating NIR activation, pH responsiveness, and AIE properties, DHTPA presents a precise and efficient antibacterial therapeutic strategy, offering an innovative solution for the clinical management of bacterial infections.