Sulfonium-Based Polymers: Underestimated Moieties for Structural Modification in Versatile Bioapplications

Polysulfoniums, sulfur-rich cationic polymers with trivalent sulfonium motifs, are promising biomaterials due to their high charge density, structural flexibility, and biocompatibility. This review highlights recent synthetic strategies: main-chain polymers via thiol-ene/epoxy click chemistry and pendant functionalization using ROMP, ROP, or RAFT polymerization, alongside postpolymerization alkylation. Their sulfonium groups selectively disrupt anionic microbial membranes, enabling broad-spectrum antibacterial action against pathogens like MRSA without inducing resistance. Stimuli-triggered dissociation enhances intracellular delivery, bolstering efficacy while reducing toxicity. These polymers also stabilize protein via sulfonium-π interactions and enable targeted therapies though zwitterionic or covalent architectures. The tunable UCST/LCST behavior and anion/pH responsiveness support smart hydrogels for wound healing and biofilm removal. Compared to ammonium and phosphonium analogs, polysulfoniums offer superior biocompatibility and membrane disruption, making them ideal for antimicrobial coatings, gene therapy, and cancer treatment. This interdisciplinary synergy between polymer science and biotechnology underscores their potential to address critical challenges in healthcare and materials science.