Phenylboronic Acid-Modified Polyethyleneimine: A Glycan-Targeting Anti-Biofilm Polymer for Inhibiting Bacterial Adhesion to Mucin and Enhancing Antibiotic Efficacy

Bacterial biofilms present significant therapeutic challenges due to their resistance to conventional antimicrobial treatment. Mucins typically serve as a protective barrier against pathogens, yet certain bacteria, such as <i>Pseudomonas aeruginosa</i> (<i>P. aeruginosa</i>), can exploit these glycoproteins as attachment sites for biofilm formation. This study introduces boronic acid-functionalized polyethyleneimine (PEI-BA) as a promising antibiofilm agent that effectively blocks bacterial adhesion to mucin-rich surfaces. Through the multivalent presentation of boronic acid groups, PEI-BA reversibly forms boronate ester bonds with mucin glycans, creating a protective barrier. Our findings show that PEI-BA prevents bacterial attachment through a nonbactericidal mechanism, potentially reducing the risk of resistance development. Notably, PEI-BA synergizes with a conventional antibiotic, tobramycin, significantly enhancing biofilm inhibition compared to either treatment alone. Systematic evaluation of PEI-BA formulations identified optimal functionalization levels, balancing glycan-binding capability with solubility. From a biomaterials design perspective, we demonstrate how rational polymer modification can transform a potent but cytotoxic antimicrobial agent (i.e., PEI) into a safe and effective antibiofilm material, opening further possibilities for managing biofilm-associated infections in clinical settings. This work establishes boronic acid-based nanomaterials as promising candidates for biofilm prevention and antibiotic enhancement, particularly in conditions like cystic fibrosis, where mucin-bacterial interactions contribute to disease progression.