Fan Wenjie, Han Haijie, Lu Zhouyu, Huang Yue, Zhang Yin, Chen Yaoyao, Zhang Xiaobo, Ji Jian, Yao Ke
Eye Center, the Second Affiliated Hospital, School of Medicine Zhejiang University Hangzhou People's Republic of China.
Zhejiang Provincial Key Lab of Ophthalmology, the Second Affiliated Hospital, School of Medicine Zhejiang University Hangzhou People's Republic of China.
Bioeng Transl Med. 2022 Aug 4;8(1):e10380. doi: 10.1002/btm2.10380. eCollection 2023 Jan.
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 (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.
细菌性角膜炎若不及时进行有效治疗,可导致眼内感染甚至失明。目前,抗生素在临床上的滥用促使了耐药菌的产生。由于杀菌效率不足且易诱导细菌耐药,基于传统抗生素滴眼液的角膜炎治疗方法受到了极大限制。因此,开发一种有效的细菌性角膜炎治疗策略具有重要意义。在本研究中,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,并在低温环境下诱导局部高温以杀死细菌。在近红外(NIR)照射下,EPL@PDA NPs悬浮液对体外MRSA的杀菌效率高达99.96%。EPL@PDA介导的aPTT在治疗MRSA引起的角膜炎方面表现出强大的抗菌效果,对角膜上皮细胞毒性小且生物相容性良好。总之,本研究中的细菌靶向aPTT平台为MRSA引起的难治性细菌性角膜炎的治疗提供了一种有前景的方法。