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

Area of Science:

• Materials Science
• Nanotechnology
• Antimicrobial Research

Background:

• Antimicrobial resistance necessitates novel therapeutic strategies.
• Membrane-active antimicrobial materials offer a promising approach.
• Nanoparticle morphology can influence biological activity.

Purpose of the Study:

• To synthesize and characterize membrane-active antimicrobial nanoparticles with controlled morphologies.
• To investigate the impact of nanoparticle shape on antibacterial efficacy and selectivity.
• To explore the mechanism of action of these antimicrobial nanostructures.

Main Methods:

• Synthesis of block copolymers (BCPs) with crystallizable and antimicrobial blocks via ring-opening and photoiniferter RAFT polymerizations.
• Preparation of nanoparticles with different morphologies (nanoplatelets and spheres) using crystallization-driven self-assembly (CDSA) in different solvents (methanol and water).
• Evaluation of antibacterial activity against Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa) and hemolytic activity.
• Confirmation of the membrane permeabilization mechanism using dye-leakage assays.

Main Results:

• CDSA of deprotected BCPs yielded 2D diamond-shaped nanoplatelets in methanol and spherical nanostructures in water.
• Nanoplatelets demonstrated superior antibacterial activity against Escherichia coli and Pseudomonas aeruginosa compared to spherical nanoparticles.
• Platelets exhibited excellent selectivity, showing no hemolytic activity.
• Dye-leakage assays confirmed membrane permeabilization as the mechanism of action.

Conclusions:

• Nanoparticle shape significantly influences interaction with bacterial membranes and overall bioactivity.
• Controlled self-assembly via CDSA enables the design of highly effective and selective antimicrobial materials.
• Diamond-shaped nanoplatelets represent a promising morphology for combating Gram-negative bacterial infections.