Photosensitizer-Polypeptide Conjugate for Effective Elimination of Candida albicans Biofilm

Persistent fungal infections caused by biofilms seriously endanger human health. In this study, a photosensitizer-polypeptide conjugate (PPa-cP) comprising a photosensitizer, pyropheophorbide a (PPa), and a cationic polypeptide (cP) is readily synthesized for effective antifungal and antibiofilm treatment. Compared with free PPa, the cationic PPa-cP shows enhanced binding ability to the negatively charged surface of Candida albicans (C. albicans) through electrostatic interactions. As a result, PPa-cP exhibits effective antifungal efficiency against both C. albicans and fluconazole-resistant C. albicans in vitro under light irradiation. The minimum inhibitory concentration (MIC) of PPa-cP for both C. albicans and fluconazole-resistant C. albicans is 1 µm. In addition, PPa-cP also shows improved penetration in a C. albicans biofilm, thus effectively eliminating the C. albicans biofilm by photodynamic effects. More importantly, PPa-cP demonstrats significantly enhanced therapeutic effects in a fluconazole-resistant C. albicans-infected rat model with minimal side effects. In conclusion, the current work presents an effective strategy to combat biofilm infections associated with biomedical equipment.