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

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.