Enzyme-Triggered Polyelectrolyte Complex for Responsive Delivery of α-Helical Polypeptides to Optimize Antibacterial Therapy
Liuxuan Li, Ruoxue Wang, Bo Zhao, Bowen Yin, Huijuan Zhang, Chunyong Liang, Xiuli Hu
Abstract
Responsive nanomaterials hold significant promise in the treatment of bacterial infections by recognizing internal or external stimuli to achieve stimuli-responsive behavior. In this study, we present an enzyme-responsive polyelectrolyte complex micelles (PTPMN) with α-helical cationic polypeptide as a coacervate-core for the treatment of Escherichia coli ( E. coli ) infection. The complex was constructed through electrostatic interaction between cationic poly(glutamic acid) derivatives and phosphorylation-modified poly(ethylene glycol)- b -poly(tyrosine) (PEG- b -PPTyr) by directly dissolving them in aqueous solution. The cationic polypeptide adopted α-helical structure and demonstrated excellent broad-spectrum antibacterial activity against both Gram-negative and Gram-positive bacteria, with a minimum inhibitory concentration (MIC) as low as 12.5 μg mL –1 against E. coli . By complexing with anionic PEG- b -PPTyr, the obtained complex formed β-sheet structures and exhibited good biocompatibility and low hemolysis. When incubated in a bacterial environment, the complex cleaved its phosphate groups triggered by phosphatases secreted by bacteria, exposing the highly α-helical conformation and restoring its effective bactericidal ability. In vivo experiments confirmed accelerated healing in E. coli -infected wounds.