Shining Light on Multidrug-Resistant Bacterial Infections: Rational Design of Multifunctional Organosilver-Based AIEgen Probes as Light-Activated Theranostics for Combating Biofilms and Liver Abscesses

Abstract

The intricate environment of biofilms provides a heaven for bacteria to escape antibiotic eradication, leading to persistent chronic infections. Therefore, it is urgently needed to develop effective therapies to combat biofilm-associated infections. To address this problem, a series of antimicrobial agents are designed and synthesized utilizing triphenylamine imidazole silver complexes (TPIMS). Due to the photoactivated release of Ag+ coupled with aggregation-induced emission (AIE) properties and efficient 1O2 generation, TPIMS exhibits excellent visual diagnostic capabilities and potent broad-spectrum antimicrobial activity, showing antimicrobial efficacy against both Gram (+) and Gram (−) bacteria. Additionally, TPIMS shows extraordinary antibacterial performance and biofilm resistance against methicillin-resistant Staphylococcus aureus (MRSA), with reduced potential for resistance thanks to the synergistic effect of phototoxicity and dark toxicity. Notably, among the TPIMS variants tested, TPIMS-8 has demonstrated exceptional curative ability against resistant bacterial biofilm infections in vivo with minimal side effects. Furthermore, it is applied to clinical samples from infected patients and the results indicated that TPIMS-8 is able to achieve excellent bacterial-specific detection and superior killing of drug-resistant bacteria even in complex systems, demonstrating its great potential for clinical applications. This study presents a promising foundation for the development of advanced antimicrobial therapeutics targeting multidrug-resistant bacteria and biofilm-associated infections.