Photosensitizer‐Polypeptide Conjugate with Synergistic Antibacterial Efficacy

Abstract Recently, continuous emergence of resistant bacteria has appeared as one of the most serious threats to human health. Therefore, systematic exploration of new antibacterial materials is of guiding significance. In this study, a series of photosensitizer‐polypeptide conjugate (PPa‐cP) is readily synthesized through simple ring‐opening reactions to realize the synergistic antibacterial effects on Staphylococcus aureus ( S. aureus ) and methicillin‐resistant S. aureus (MRSA) under light irradiation. Compared with free PPa, the cationic PPa‐cP shows enhanced binding ability with the negative surface of S. aureus through electrostatic interaction, exhibiting effective antibacterial activity against both S. aureus and MRSA in vitro under light irradiation. Among the synthesized PPa‐cP, PPa‐cP5 with the degree of polymerization of 37 and modified with a 1‐methylimidazole side group exhibits the best antibacterial activity with a minimum inhibitory concentration value of 2 µ m without light irradiation and 0.25 µ m with light irradiation. Moreover, PPa‐cP5 shows good hemocompatibility. The above‐mentioned results elucidate that the positively charged PPa‐cP5 can significantly increase the efficiency of photodynamic therapy and effectively eradicate S. aureus biofilm due to its potent penetration ability into S. aureus biofilms. Overall, the present study establishes an efficient strategy for the treatment of S. aureus and S. aureus biofilm infections.