Ye Zhang, Yuanhan Zhong, Yanjun Wang, Hongzhu Wang, Shihao Hong, Yufei Zhang, Hongyu Wang, Ruiyao Wang, Jie Li, S. Y. Huang, Xinge Zhang
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 Zn 2+ 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 Zn 2+ 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.