Poly(l-ornithine)-Grafted Zinc Phthalocyanines as Dual-Functional Antimicrobial Agents with Intrinsic Membrane Damage and Photothermal Ablation Capacity.

Abstract

Multifunctional antimicrobial peptides that combine the intrinsic microbicidal property of cationic polypeptide chains and additional antibacterial strategy hold promising applications for the treatment of infections caused by antibiotic-resistant bacteria, especially "superbugs". In the present study, star-shaped copolymers ZnPc-g-PLO with a zinc phthalocyanine (ZnPc) core and four poly(l-ornithine) (PLO) arms were designed, synthesized, and evaluated as dual-functional antimicrobial agents, that is, intrinsic membrane damage and photothermal ablation capacity. In an aqueous solution, amphiphilic ZnPc-g-PLO molecules self-assemble into nanosized polymeric micelles with an aggregated ZnPc core and star-shaped PLO periphery, where the ZnPc core exhibits appreciable aggregation-induced photothermal conversion efficiency. In the absence of laser irradiation, ZnPc-g-PLO micelles display potent and broad-spectrum antibacterial activities via physical bacterial membrane disruption as a result of the high cationic charge density of the star-shaped PLO. Upon laser irradiation, significant improvement in bactericidal potency was realized due to the efficacious photothermal sterilization from the ZnPc core. Notably, ZnPc-g-PLO micelles did not induce drug-resistance upon subinhibitory passages. In summary, dual-functional ZnPc-g-PLO copolymers can serve as promising antibacterial agents for the treatment of infectious diseases caused by antibiotic-resistant bacteria.