A Targeted Photosensitizer Mediated by Visible Light for Efficient Therapy of Bacterial Keratitis

Yu, C (Yu, Cong) 1Gao, YC (Gao, Yingchao) 1Zhang, YL (Zhang, Yanlong) 2Wang, J (Wang, Jie) 1Zhang, YF (Zhang, Yufei) 1Li, J (Li, Jie) 1Zhang, XX (Zhang, Xinxing) 1Wu, ZM (Wu, Zhongming) 3, 4Zhang, XG (Zhang, Xinge) 1

BIOMACROMOLECULES, 2021, 22(9): 3704-3717

DOI 10.1021/acs.biomac.1c00461

Abstract

Bacterial keratitis is a serious bacterial infection of the cornea that can cause sight loss in severe cases because of the sharp decline of efficacious antibiotics. Herein, a targeted photosensitizer based on BODIPY severing as a photobactericidal agent was developed for treating bacterial keratitis. The water solubility of the material was as high as 10 mg/mL, which was attributable to the introduction of pathogen-targeting galactose and fucose. The photosensitizer was able to preferentially bind Pseudomonas aeruginosa instead of mammalian cells and trigger the aggregation of bacteria, which ultimately facilitated effective pathogen ablation upon the generation of reactive oxygen species (ROS) via laser irradiation. Photoexcited targeted photosensitizers can promote wound healing by eradicating P. aeruginosa in rat eyes and reducing the inflammatory response, thus exhibiting the significant therapeutic effect on bacterial keratitis. We also performed molecular level mechanistic studies using the unique field-induced droplet ionization mass spectrometry methodology and confirmed that the generated ROS were mainly singlet oxygen that caused lipid peroxidation (Type II mechanism). We anticipate that the targeted photosensitizer will have great potential in the application of clinical photodynamic therapy to ocular infection.