Cationic conjugated polymers with tunable hydrophobicity for efficient treatment of multidrug-resistant wound biofilm infections

Abstract

Biofilm-associated infections arising from antibiotic-resistant bacteria pose a critical challenge to global health. We report the generation of a library of cationic conjugated poly(phenylene ethynylene) (PPE) polymers featuring trimethylammonium terminated sidechains with tunable hydrophobicity. Screening of the library identified an amphiphilic polymer with a C₁₁ hydrophobic spacer as the polymer with the highest antimicrobial efficacy against biofilms in the dark with excellent selectivity. These polymers are highly fluorescent, allowing label-free monitoring of polymer-bacteria/biofilm interactions. The amphiphilic conjugated polymer penetrated the biofilm matrix in vitro and eradicated resident bacteria through membrane disruption. This C₁₁ polymer was likewise effective in an in vivo murine model of antibiotic-resistant wound biofilm infections, clearing >99.9 % of biofilm colonies and efficient alleviation of biofilm-associated inflammation. The results demonstrate the therapeutic potential of the fluorescent conjugated polymer platform as a multi-modal antimicrobial and imaging tool, surpassing conventional antimicrobial strategies against resilient biofilm infection.