This study presents the development of biocompatible Ru(II)-based photo-antibiotics that increase oxidative stress via ROS generation (both type I and type II pathways) and NADH oxidation, killing bacterial cells and eradicating bacterial biofilm with a novel mechanism. Moreover, the lead photo-antibiotics eradicated the gram-negative bacterial colony from the infected wounds in a rat model within 3 days and healed the wound completely within 9 days, bridging the gap between aPDT outcomes and clinical trials.

Abstract

Three novel Ru(II)-based photoantibiotics, viz., [Ru(phtpy)(N,N,N)₂](PF₆)₂, where N,N,N = 4′-phenyl-2,2′:6′,2″-terpyridine (phtpy, Ru1), 4-([2,2′:6′,2′′-terpyridin]-4′-yl)-N,N-dimethylaniline (NMe₂tpy, Ru2), trifluoromethylphenyl)-2,2′:6′,2′′-terpyridine (CF₃tpy, Ru3) were developed with excellent photostability for visible light-activated antibacterial activities and infective wound healing. Ru1-Ru3 exhibited an absorption in the 400–600 nm range, beneficial for antibacterial photodynamic therapy (aPDT) application. Upon visible light exposure (400-700 nm), Ru1-Ru3 inhibited bacterial growth of Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis), due to the effects of oxidative stress via ROS generation and photo-oxidation of NADH. Ru3 was identified as a lead antibiotic that further showed antibiofilm activities against E. coli under visible light exposure. Ru3 was found to be biocompatible against rat red blood cells and human embryonic kidney cells. Ru3 + light promoted rapid healing of infected wounds within 9 days in an E. coli-induced rat model, highlighting its potential future use in healthcare.