Cationic Peptidopolysaccharide Shows Excellent Antimicrobial Efficacy with Good Biocompatibility

Cationic antimicrobial peptides (AMPs) and polymers are active against many multi-drug resistant (MDR) bacteria but only a limited number of these compounds are in clinical use due to their unselective toxicity. The typical strategy for achieving selective antibacterial efficacy with low mammalian cell toxicity is through balancing the ratio of cationicity to hydrophobicity. Herein, we report a cationic nanoparticle self-assembled from chitosan-graft-oligolysine (CSM5-K5) chains with ultra-low molecular weight (1450 Daltons) that selectively kills bacteria. Further, hydrogen bonding rather than the typical hydrophobic interaction causes the polymer chains to be aggregated together in water into small nanoparticles (with about 37nm hydrodynamic radius) to concentrate the cationic charge of the lysine. When complexed with bacterial membrane, these cationic nanoparticles synergistically cluster anionic membrane lipids and produce greater membrane perturbation and antibacterial effect than would be achievable by the same quantity of charge if dispersed in individual copolymer molecules in solution.