Polymeric nanoantibiotics based on two orthogonal binding motifs coalesce with bacterial matter

Addressing the growing concern of antibiotic-resistant bacteria, we developed a series of novel polymeric nanoantibiotics with a dual-war- head system that induces physical lysis upon copolymer coalescence with bacterial matter. These polymers are equipped with two orthogonal binding motifs that form electrostatic interactions and dynamic covalent complexes on bacterial surfaces and exhibit potent antibacterial activity against gram-positive and gram-negative bacteria. The effect of the chemical composition and architecture of copolymers incorporating phenylboronic acid and quarternary ammo- nium groups on the antimicrobial activities was systematically examined. This work expands the current chemical repertoire to combat antimicrobial re- sistance by polymeric nanoantibiotics with a unique mode of action.