A Polypeptosome Spray To Heal Antibiotic-Resistant Bacteria-Infected Wound by Photocatalysis-Induced Metabolism-Interference

With the booming antimicrobial drug resistance worldwide, traditional antibacterial agents (e.g., antibiotics) are usually powerless against superbug. Targeting antibacterial pathways different from traditional antibiotics could be an effective approach to treating wounds with a resistant bacterial infection. In this work, an antibacterial polymersome was developed to physically induce bacterial membrane damage and interfere with bacterial metabolism. First, we synthesized an antibacterial poly(ε-caprolactone)-block-poly(glutamic acid)-block-poly(Lys-stat-Phe) copolymer, which was then self-assembled into polypeptosome with the amplification of surface positive charges to disrupt bacterial membranes. In addition, the polypeptosome was further decorated with photocatalytic bismuth sulfide (Bi₂S₃) nanoparticles as a photocatalyst to interfere with reduced nicotinamide adenine dinucleotide (NADH) conversion. Specifically, near-infrared light generated free electrons from Bi₂S₃ nanoparticles could effectively interfere with NADH homeostasis to induce antibiotic-resistant bacteria death, as verified by transcriptome sequence analysis. Moreover, effective healing of antibiotic-resistant bacteria-infected wounds of mice was achieved with a spray of polypeptosome dispersion. Overall, we provided a fresh strategy to integrate bacterial membrane damage and metabolism interference functions within antibacterial polymersomes for healing antibiotic-resistant bacteria-infected wound.