Simple Surface Charge Engineering of Conjugated Polymer Nanoparticles for Potent Dual-Mode Photoinactivation of Resistant Bacteria and Biofilms

The emergence of antibiotic-resistant bacteria, particularly in biofilm-associated infections, poses a severe threat to global health. Light-activated therapies, such as photodynamic inactivation (PDI) and photothermal therapy (PTT), offer promising alternatives. This study describes a straightforward self-assembly approach for producing positively charged core/shell conjugated polymer nanoparticles ( F8BT-PtOEP@PFN NPs ) to improve the effectiveness of antimicrobial phototherapy. The core consists of poly(9,9-dioctylfluorene- alt -benzothiadiazole) ( F8BT ) doped with the photosensitizer platinum(II) octaethylporphyrin ( PtOEP ), while the shell is made up of a cationic polyfluorene derivative ( PFN ). These nanoparticles exhibit a remarkable combination of a suitable singlet oxygen quantum yield (Φ Δ = 0.23), an outstanding photothermal conversion efficiency (η = 0.95), and excellent photostability. The cationic PFN shell dramatically enhances electrostatic binding to methicillin-resistant Staphylococcus aureus (MRSA, a Gram-positive bacterium), as confirmed by flow cytometry and supported by comparative ζ-potential measurements of bacteria before and after NP incubation. In planktonic cultures, F8BT-PtOEP@PFN NPs exhibited a bactericidal effect under blue light, achieving a >4 log reduction in colony-forming units, whereas the uncoated (anionic) NPs ( F8BT-PtOEP NPs ) only had a bacteriostatic effect. More importantly, the core/shell NPs were highly effective against mature MRSA biofilms, significantly reducing biomass, metabolic activity, and exopolysaccharide matrix integrity, as demonstrated by crystal violet, MTT, and calcofluor white assays, respectively. The core/shell NPs also exhibited excellent biocompatibility with eukaryotic cells. This study highlights the profound impact of simple surface engineering on the effectiveness of conjugated polymer nanoparticles in potent PDI–PTT against resilient bacterial biofilms. To our knowledge, these combined features (cationic conjugated polymer NPs with a Φ Δ of 0.23 and an η of 0.95 for dual PDI–PTT action) have not previously been achieved simultaneously in a single nanoparticle system.