Elaborately Engineered Aggregation‐Induced Emission Antibacterial Agents: Negligible Living Cell Invasiveness, Efficient Bacterial Biofilm Inhibition and Promoting Infected Wound Healing

Abstract Developing versatile photosensitizers capable of selectively eliminating pathogens over normal cells is an appealing yet highly challenging task. Herein, a novel strategy by exploiting the cationic and amphiphilic synergistic mechanism is introduced to synthesize four aggregation‐induced emission (AIE)‐active cationic antibacterial photosensitizers (PSs) TSPy‐CH 3 , MeO‐TSPy‐Bu , MeO‐TSPy‐Va and MeO‐TSPy‐CH 3 . The four PSs generated both type I and type II reactive oxygen species (ROS) under white light irradiation. They can quickly stain Staphylococcus aureus ( S. aureus ) in 15 min, but exhibited different Escherichia coli ( E.coil ) affinity and living cell invasiveness. The four PSs caused devastating killing to S. aureus and methicillin‐resistant Staphylococcus aureus (MRSA) at extremely low drug doses and significantly inhibited biofilm formation of drug‐resistant strains by synergistic photocytotoxicity and inherent dark toxicity. Their low antibacterial concentrations and minimal invasiveness toward normal cells collectively ensured biosafety. MeO‐TSPy‐CH 3 with moderate Clog P value stands out from others by virtues of most reliable biosafety, broad‐spectrum bactericidal performance, and excellent biofilm inhibition ability. In vivo studies on bacteria‐infected wounds confirmed that MeO‐TSPy‐CH 3 reduced inflammation, promoted angiogenesis, and accelerated wound recovery, achieving comparable therapeutic outcomes to vancomycin. This work provides enlightenment for designing novel antibacterial phototherapy agents to overcome key limitations such as unpredictable biosafety risk, inadequate antibacterial potency, and poor anti‐biofilm performance.