A Polypeptosome\nSpray To Heal Antibiotic-Resistant\nBacteria-Infected Wound by Photocatalysis-Induced Metabolism-Interference

With\nthe booming antimicrobial drug resistance worldwide,\ntraditional\nantibacterial agents (e.g., antibiotics) are usually powerless against\nsuperbug. Targeting antibacterial pathways different from traditional\nantibiotics could be an effective approach to treating wounds with\na resistant bacterial infection. In this work, an antibacterial polymersome\nwas developed to physically induce bacterial membrane damage and\ninterfere with bacterial metabolism. First, we synthesized an antibacterial\npoly(ε-caprolactone)-<i>block</i>-poly(glutamic acid)-<i>block</i>-poly(Lys-<i>stat</i>-Phe) copolymer, which\nwas then self-assembled into polypeptosome with the amplification\nof surface positive charges to disrupt bacterial membranes. In addition,\nthe polypeptosome was further decorated with photocatalytic bismuth\nsulfide (Bi<sub>2</sub>S<sub>3</sub>) nanoparticles as a photocatalyst\nto interfere with reduced nicotinamide adenine dinucleotide (NADH)\nconversion. Specifically, near-infrared light generated free electrons\nfrom Bi<sub>2</sub>S<sub>3</sub> nanoparticles could effectively interfere\nwith NADH homeostasis to induce antibiotic-resistant bacteria death,\nas verified by transcriptome sequence analysis. Moreover, effective\nhealing of antibiotic-resistant bacteria-infected wounds of mice was\nachieved with a spray of polypeptosome dispersion. Overall, we provided\na fresh strategy to integrate bacterial membrane damage and metabolism\ninterference functions within antibacterial polymersomes for healing\nantibiotic-resistant bacteria-infected wound.