Bacterial keratitis can lead to intraocular infection and even blindness without prompt and potent treatments. Currently, clinical abuse of antibiotics encouraged the evolution of resistant bacteria. Conventional antibiotic eye drops based keratitis treatment has been heavily restricted due to the lack of bactericidal efficiency and easy induction of bacterial resistance. Hence, developing an effective treatment strategy for bacterial keratitis is of great significance. In this work, we investigated ε-poly-l-lysine (EPL)-modified polydopamine (PDA) nanoparticles (EPL@PDA NPs)-mediated antibacterial photothermal therapy (aPTT), to cope with methicillin-resistant Staphylococcus aureus (MRSA)-induced keratitis. The surface modification of cationic peptide EPL enables EPL@PDA NPs to specifically target negatively charged MRSA and induces local hyperthermia to kill the bacteria under low ambient temperature. Under near-infrared (NIR) irradiation, the sterilization efficiency of EPL@PDA NPs suspension for MRSA in vitro was up to 99.96%. The EPL@PDA-mediated aPTT presented potent antibacterial efficacy in treating MRSA-induced keratitis with little corneal epithelial cytotoxicity and good biocompatibility. In conclusion, the bacterial-targeting aPTT platform in this work provides a prospective method for the management of MRSA-induced refractory bacterial keratitis.

中文翻译：

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ε-聚-L-赖氨酸修饰的聚多巴胺纳米粒用于耐药细菌性角膜炎的靶向光热治疗

如果没有及时有效的治疗，细菌性角膜炎可导致眼内感染甚至失明。目前，抗生素的临床滥用助长了耐药菌的进化。由于缺乏杀菌效率和容易诱导细菌耐药性，传统的基于抗生素滴眼液的角膜炎治疗受到严重限制。因此，制定有效的细菌性角膜炎治疗策略具有重要意义。在这项工作中，我们研究了ε-聚-l-赖氨酸（EPL）修饰的聚多巴胺（PDA）纳米颗粒（EPL@PDA NPs）介导的抗菌光热疗法（aPTT），以应对耐甲氧西林金黄色葡萄球菌(MRSA) 引起的角膜炎。阳离子肽 EPL 的表面修饰使 EPL@PDA NPs 能够特异性靶向带负电荷的 MRSA，并诱导局部热疗以在低环境温度下杀死细菌。在近红外 (NIR) 照射下，EPL@PDA NPs 悬浮液对 MRSA 的体外灭菌效率高达 99.96%。EPL@PDA 介导的 aPTT 在治疗 MRSA 诱导的角膜炎方面表现出强大的抗菌功效，具有极小的角膜上皮细胞毒性和良好的生物相容性。总之，这项工作中的细菌靶向 aPTT 平台为 MRSA 诱导的难治性细菌性角膜炎的管理提供了一种前瞻性的方法。