Main-Chain Sulfonium-Containing Homopolymers with Negligible Hemolytic Toxicity for Eradication of Bacterial and Fungal Biofilms

Abstract

Antimicrobials against planktonic cells and established biofilms at low doses are in increasing demand to tackle antibiotic-resistant biofilm infections. As a promising alternative to antibiotics, cationic polymers can effectively kill planktonic microbes but usually require high concentrations to eradicate the established biofilms. Herein, we developed a series of sulfonium-based homopolymers with cationic sulfoniums and alkane spacers in the main chain. These polysulfoniums presented effective activity against planktonic fungi (<i>Candida albicans</i>) and bacteria (<i>Escherichia coli</i> and <i>Staphylococcus aureus</i>) with minimum inhibition concentrations (MICs) of 0.5-32 μg/mL, and the optimal composition can provide an 80-90% reduction in biofilm mass and >99% killing of <i>Candida albicans</i> and <i>Escherichia coli</i> cells in 3-day mature biofilms at 2 × MIC as well as steadily low hemolytic toxicity. The influence of amphiphilicity and charge density of polysulfonium homopolymers on their antimicrobial activity against planktonic microbes and mature biofilms was investigated to provide insights for effective antimicrobial polymer design.