Self-Assembled Ce6-Peptide Nanoparticles Enhance NO Production and Photodynamic Therapy against Bacterial Infections

The alarming rise of antibiotic resistance necessitates the development of innovative antibacterial strategies. Photodynamic therapy (PDT) has emerged as a promising alternative, but its efficacy is often hindered by poor photosensitizer solubility and potential biotoxicity. To overcome these limitations, we designed a peptide-photosensitizer conjugate, chlorin e6-RFSSFR ( Ce6-RFSSFR ), which self-assembles into nanoparticles with improved photodynamic properties. This conjugate leverages arginine residues as nitric oxide (NO) donors upon light activation, facilitating localized NO production and amplifying the antibacterial effects of PDT. Our in vitro and in vivo evaluations demonstrate the superior therapeutic potential of Ce6-RFSSFR over conventional Ce6, with enhanced antibacterial efficacy, remarkable wound healing promotion, and anti-inflammatory properties. These findings position Ce6-RFSSFR as a promising candidate for clinical applications in bacterial infection treatment and tissue regeneration, offering a valuable tool in the fight against antimicrobial resistance.