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

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A Targeted Photosensitizer Mediated by Visible Light for Efficient Therapy of Bacterial Keratitis
Biomacromolecules ( IF 5.5 ) Pub Date : 2021-08-12 , DOI: 10.1021/acs.biomac.1c00461
Cong Yu ₁ , Yingchao Gao ₁ , Yanlong Zhang ₂ , Jie Wang ₁ , Yufei Zhang ₁ , Jie Li ₁ , Xinxing Zhang ₁ , Zhongming Wu ₃ , Xinge Zhang ₁

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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.

中文翻译：

一种用于有效治疗细菌性角膜炎的可见光介导的靶向光敏剂

细菌性角膜炎是一种严重的角膜细菌感染，由于有效抗生素的急剧下降，在严重的情况下会导致视力丧失。在此，开发了一种基于 BODIPY 切断作为光杀菌剂的靶向光敏剂，用于治疗细菌性角膜炎。该材料的水溶性高达 10 mg/mL，这是由于引入了靶向病原体的半乳糖和岩藻糖。光敏剂能够优先结合铜绿假单胞菌而不是哺乳动物细胞并触发细菌聚集，最终通过激光照射产生活性氧 (ROS) 促进有效的病原体消融。光激发靶向光敏剂可通过根除促进伤口愈合P. aeruginosa在大鼠眼中减少炎症反应，从而对细菌性角膜炎表现出显着的治疗效果。我们还使用独特的场诱导液滴电离质谱方法进行了分子水平的机理研究，并确认产生的 ROS 主要是导致脂质过氧化的单线态氧（II 型机制）。我们预计靶向光敏剂将在临床光动力疗法应用于眼部感染方面具有巨大潜力。

更新日期：2021-09-13

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