Carbonized nanogels for simultaneous antibacterial and antioxidant treatment of bacterial keratitis
Carbonized nanogels for simultaneous antibacterial and antioxidant treatment of bacterial keratitis
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DOI：
10.1016/j.cej.2021.128469
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发表时间：
2021-01-22
影响因子：
15.1
通讯作者：
Lai, Jui-Yang
中科院分区：
文献类型：
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作者：
Lin, Hung-Yun;Wang, Sin-Wen;Lai, Jui-Yang
为了防止视力丧失，严重细菌性角膜炎（BK）的临床治疗需要同时补救由细菌感染及其诱导的角膜氧化应激/炎症引起的损伤。在这里，我们已经开发了一种一步法合成生物槲皮素（Qu）和赖氨酸（Lys）作为具有抗菌和抗氧化特性的双功能药物用于局部BK治疗的纳米凝胶（CNG）。这些通过干热合成的Qu/LysCNG继承并放大了两种天然产物的优点，包括优异的抗氧化能力和高正电荷。Qu/Lys-CNG对非多药耐药细菌（大肠杆菌、铜绿假单胞菌、金黄色葡萄球菌、沙门氏菌）以及多药耐药细菌（耐甲氧西林金黄色葡萄球菌）显示出广谱抑菌作用。由Qu/Lys-CNG引起的细菌外围结构的解体是由于它们与细菌膜的强烈且特异性的相互作用。体外细胞毒性和溶血试验以及体内角膜生物相容性评价显示Qu/Lys-CNG作为眼用滴剂制剂中的安全纳米药物具有良好的生物相容性。此外，Qu/Lys-CNG可以通过上皮紧密连接开口渗透到角膜中，从而对S.金黄色葡萄球菌引起的兔角膜炎。我们的研究结果表明，Qu/Lys-CNG可能是一种有效的双功能药物，用于临床应用，以治疗细菌性眼病。
To prevent visual loss, clinical therapy of severe bacterial keratitis (BK) demands simultaneous remedying of the damage caused by bacterial infection and its induced oxidative stress/inflammation of the cornea. Here, we have developed a one-step method to synthesize carbonized nanogels (CNGs) from biogenic quercetin (Qu) and lysine (Lys) as a bifunctional agent with antibacterial and antioxidant properties for topical BK therapy. These Qu/LysCNGs synthesized by dry heating inherit and amplify the advantages of two natural products, including excellent antioxidant capacity and high positive charge. The Qu/Lys-CNGs display broad-spectrum bacteriostatic effects against non-multidrug-resistant bacteria, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella enteritidis, and also against multidrug-resistant bacteria, methicillin-resistant Staphylococcus aureus. Disintegration of peripheral structures of the bacteria caused by Qu/Lys-CNGs is due to their strong and specific interaction with bacterial membranes. In vitro cytotoxicity and hemolysis assays and in vivo corneal biocompatibility evaluations revealed good biocompatibility of Qu/Lys-CNGs as a safe nanomedicine in ophthalmic drop formulation. Furthermore, the Qu/Lys-CNGs can penetrate into the cornea via epithelial tight junction opening, thereby exerting superior antibacterial and antioxidant therapeutic effects against S. aureus-induced keratitis in rabbits. Our results indicate Qu/Lys-CNGs could be an effective bifunctional agent for clinical applications to treat bacterial ocular diseases.