Modular Polymers With Tuneable Charge and Amphiphilicity for Effective Antimicrobial Photodynamic Therapy.

A modular synthetic platform delivers polymers that integrate, within a single architecture, a hydrophilic backbone, hydrophobic side chains, charged groups, and photoactive agents for antimicrobial photodynamic therapy (aPDT). Ruthenium complexes are used as representative photoactive systems, and clinical strains of Pseudomonas aeruginosa, Staphylococcus aureus, and Escherichia coli serve as bacterial targets. Two complementary strategies are deployed in parallel within a single design framework: free-radical copolymerisation of acrylic ruthenium-photosensitiser monomers, and post-polymerisation modification of a pentafluorophenyl-acrylate precursor with amine-functionalised ruthenium complexes. Both routes allow independent tuning of composition, solubility, amphiphilic balance, and net charge, a set of properties that together govern the polymers' interaction with bacterial surfaces. The approach yields a library of seven water-dispersible, amphiphilic polymer-metal hybrids. Benchmarked against a bare ruthenium complex, the aPDT-polymers exhibit strong UV-visible absorption, efficient reactive oxygen species production, low (photo)cytotoxicity towards human bronchial epithelial cells, and potent antibacterial activity, particularly against multidrug-resistant P. aeruginosa in planktonic and biofilm states. Multivariate clustering reveals clear guidelines for structure-activity relationships: anionic acrylic-acid-rich architectures are most effective against P. aeruginosa biofilms under saline conditions, while cationic compositions are preferential against planktonic S. aureus. The platform thus provides a rationally tuneable basis for next-generation polymer-based photoactive antimicrobials.