The alarming rise of infections caused by drug-resistant pathogens represents a critical challenge to global healthcare. Excessive antibiotic use, coupled with slow progress in new drug development, has fueled the emergence of multidrug-resistant (MDR) bacteria, rendering many conventional treatments ineffective. Compounding this issue is the ability of microbes to form biofilms on medical implants, surgical tools, hospital environments, and biological tissues. These biofilms shield bacteria from antibiotics, contributing to persistent, difficult-to-treat infections.
To address these challenges, there is an urgent need for alternative antimicrobial strategies with mechanisms distinct from traditional antibiotics. Cationic antimicrobial peptides (CAMPs), inspired by natural host-defense molecules, have shown promise due to their membrane-disrupting action. However, issues such as toxicity toward mammalian cells and poor stability have limited their clinical translation.
In response, synthetic antimicrobial polymers have gained attention due to their tunable composition, improved stability, and long-term activity. In particular, polymers bearing quaternary ammonium groups are widely known for their antimicrobial properties. Yet, resistance concerns have driven interest toward alternative cationic systems.
Sulfonium-functionalized polymers, though less explored, offer unique membrane-disrupting potential and may circumvent limitations of traditional systems. This project proposes the design of pendant-modified amphiphilic polymers combining both sulfonium and quaternary ammonium groups within a single framework. Such dual-functional polymers are expected to deliver potent, broad-spectrum antimicrobial activity, reduced toxicity, and improved selectivity—addressing critical gaps in next-generation antimicrobial materials.
Research Focus and Novelty
The present work aims to address this critical gap by developing a new class of pendant-modified amphiphilic polymers incorporating both sulfonium and quaternary ammonium cationic functionalities. Through a modular synthetic approach involving controlled radical polymerization, thiol-ene click chemistry, and post-polymerization alkylation, these polymers will be designed to exhibit tunable hydrophilic-hydrophobic balance, enhanced membrane-disrupting activity, and minimized mammalian cytotoxicity.
A key feature of this work is the dual incorporation of sulfonium and ammonium groups within a single polymer backbone, enabling synergistic antimicrobial action with reduced risk of resistance development. Special emphasis will be placed on evaluating these materials against both Gram-positive pathogens, including M. smegmatis, and challenging Gram-negative strains, such as E. coli.
By advancing the development of structurally versatile, dual-cationic, antimicrobial polymers, this project seeks to contribute to the urgent global demand for next-generation, highly effective, and safe antimicrobial materials.