Antibacterial Nanoplatelets via Crystallization-Driven Self-Assembly of Poly(l-lactide)-Based Block Copolymers

Membrane-active antimicrobial materials are promising substances to fight antimicrobial resistance. Herein, crystallization-driven self-assembly (CDSA) is employed for the preparation of nanoparticles with different morphologies, and their bioactivity is explored. Block copolymers (BCPs) featuring a crystallizable and antimicrobial block were synthesized using a combination of ring-opening and photoiniferter RAFT polymerizations. Subsequently formed nanostructures formed by CDSA could not be deprotected without degradation of the structures. CDSA of deprotected BCPs yielded 2D diamond-shaped nanoplatelets in MeOH, while spherical nanostructures were observed for assembly in water. Platelets exhibited improved antibacterial capabilities against two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa) compared to their spherical counterparts. The absence of hemolytic activity leads to the excellent selectivity of platelets. A mechanism based on membrane permeabilization was confirmed via dye-leakage assays. This study emphasized the impact of the shape of nanostructures on their interaction with bacterial cells and how a controlled assembly can improve bioactivity.