A Self-Assembled Nanophotosensitizer Effectively Inactivates Biofilm-Related Infections

Bacterial biofilm significantly hinders the penetration of antimicrobial agents, making bacterial clearance challenging and leading to persistent biofilm-associated infections. A precise combination of phototherapeutics and chemotherapy can synergistically improve the therapeutic outcome and thereby may overcome drug-resistant bacteria through a multipronged assault. Herein, a nanophotosensitizer (BHZnC) was developed through a multicomponent self-assembly strategy, incorporating phototherapeutics and antimicrobial peptides, coordinated with Zn2+ and modified with benzoxaborole-conjugated histatin-5 (BHst-5) and Chlorin e6 (Ce6). This innovative system not only effectively penetrates biofilm matrices but also prevents degradation of Hst-5 by proteases secreted by Candida albicans (C. albicans). The binding of Hst-5 with Zn2+ promotes microbial membrane fusion and rupture, thereby enhancing the bactericidal efficacy. In vivo studies demonstrate that the combination of chemotherapy and phototherapeutics exhibits a superior antibiofilm performance against a drug-resistant bacteria model attributed to their synergistic anti-infection efficacy.