D-Alanine functionalized Iridium(III) complexes as two-photon photo-antibiotics for bacteria-specific ablation in infected macrophages

The prevalence of bacterial resistance, driven by extensive antibiotic overuse, significantly threatens patient safety. Consequently, it is urgent and helpful for the clinician to develop new antibacterial therapy techniques. In this study, we designed a novel photodynamic antibacterial therapeutic strategy by functionalizing D-alanine on Iridium(III) complexes. The synergistic D-alanine metabolic labeling function and two-photon photodynamic eradication capacity of Ir(III) complexes enable bacterial imaging and elimination of bacterial pathogens within host cells. These two-photon photoantibiotics effectively inhibit bacterial biofilm formation and efficiently eliminate intracellular bacterial infections in macrophages, enabling real-time dynamic monitoring of antimicrobial efficacy. Furthermore, both in vitro and in vivo experiments demonstrated superior antibacterial performance compared to conventional antibiotics alone.