Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan, ROC.
Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung 40402, Taiwan, ROC; Biomaterials Translational Research Center, China Medical University Hospital, Taichung 40447, Taiwan, ROC; Department of Bioinformatics and Medical Engineering, Asia University, Taichung 41354, Taiwan, ROC.
J Colloid Interface Sci. 2019 Feb 15;536:112-126. doi: 10.1016/j.jcis.2018.10.041. Epub 2018 Oct 17.
Staphylococcus aureus (S. aureus) is a leading cause of keratitis worldwide and a significant threat to healthy vision. Pathological manifestations of bacterial keratitis (BK) caused by S. aureus involve stromal opacity, edema and neovascularization of an inflamed cornea, requiring immediate medical attention. Thus, S. aureus-induced keratitis is a devastating ocular infection that can lead to blindness if effective and timely treatment is not initiated. In this study, we demonstrate gelatin-capped silver nanoparticles (G-Ag NPs) as anti-infective therapeutics for the treatment of S. aureus-induced keratitis. G-Ag NPs were prepared by simple mixing of silver nitrate, maltose and gelatin. The gelatin molecules are capped in situ on the Ag NPs (∼14 nm). Compared to uncapped Ag NPs, the G-Ag NPs possess superior stability and antibacterial activity against S. aureus. We further demonstrate that G-Ag NPs possess effective inhibition of the proliferation, migration and tube formation of human umbilical vein endothelial cells, as well as strong disturbance of the angiogenesis in chick chorioallantoic membrane and rabbit corneal neovascularization. Furthermore, intrastromal administration of highly biocompatible G-Ag NPs alleviates S. aureus-induced bacterial keratitis in rabbit eyes and bacterial infection-induced corneal neovascularization. Our results demonstrate G-Ag NPs as a promising dual functional (antimicrobial and antiangiogenic) nanotherapeutic for preclinical treatment of eye-related microbial infections.
金黄色葡萄球菌（S. aureus）是全球角膜炎的主要病因，也是健康视力的重大威胁。由 S. aureus 引起的细菌性角膜炎（BK）的病理表现涉及基质混浊、炎症角膜的水肿和新生血管形成，需要立即就医。因此，金黄色葡萄球菌引起的角膜炎是一种破坏性的眼部感染，如果不及时有效治疗，可能导致失明。在本研究中，我们证明了明胶包裹的银纳米颗粒（G-Ag NPs）可作为治疗金黄色葡萄球菌诱导的角膜炎的抗感染治疗药物。G-Ag NPs 通过硝酸银、麦芽糖和明胶的简单混合制备而成。明胶分子原位覆盖在 Ag NPs（约 14nm）上。与未覆盖的 Ag NPs 相比，G-Ag NPs 具有更好的稳定性和抗金黄色葡萄球菌的抗菌活性。我们进一步证明，G-Ag NPs 对人脐静脉内皮细胞的增殖、迁移和管形成具有有效抑制作用，并强烈干扰鸡胚绒毛尿囊膜血管生成和兔角膜新生血管形成。此外，基质内给药高度生物相容的 G-Ag NPs 可减轻兔眼金黄色葡萄球菌诱导的细菌性角膜炎和细菌感染诱导的角膜新生血管形成。我们的研究结果表明，G-Ag NPs 是一种有前途的双重功能（抗菌和抗血管生成）纳米治疗药物，可用于眼部相关微生物感染的临床前治疗。
