Ir(III) Nanoaggregates as Photodynamic Antimicrobial Agents against Resistant <i>S. aureus</i> in a Wound Healing Mouse Model

The overuse of conventional antibiotics has enhanced the development of multidrug-resistant bacteria, which necessitates the development of innovative alternatives to combat bacterial infections. Antibacterial photodynamic therapy has emerged as a promising approach for the treatment of bacterial infections by inducing oxidative stress via reactive oxygen species generation. Recently, progress has been made in designing nanomaterial-based photoactive drugs that harness light to generate oxidative stress, effectively destroying bacterial cells upon irradiation. In this study, complex IrL¹ stands out as a photodynamic antimicrobial chemotherapeutic agent. IrL¹ self-assembled in culture media and demonstrated selective activity against Gram-positive <i>Staphylococcus aureus</i> with a minimum inhibitory concentration (MIC) value of 1 μg mL^-1 in the dark and 0.5 μg mL^-1 when irradiated with 390 nm light. It exhibited significant efficacy against methicillin-resistant <i>S. aureus</i> (MRSA) and vancomycin-resistant <i>S. aureus</i> (VRSA), as evidenced by MIC values ranging from 2 μg/mL. Upon irradiation, it induced oxidative stress by producing ¹O₂ and damaged the bacterial cell wall, as demonstrated by SEM and AFM imaging studies, which leads to cell death. Docking studies revealed its targeting of topoisomerase II DNA gyrase (binding energy = -14.33 kcal/mol, <i>k</i>_i = 31.15 pM), essential for bacterial survival. Time-kill assays and drug resistance studies reinforced its antimicrobial potential, and an <i>in vivo</i> evaluation demonstrated its therapeutic promise. Furthermore, the previously reported photodynamic anticancer properties of IrL¹ make it a compelling candidate for integrated therapeutic strategies, especially for cancer patients who are highly vulnerable to bacterial infections due to compromised immunity.