Kost Olga A, Beznos Olga V, Davydova Nina G, Manickam Devika S, Nikolskaya Irina I, Guller Anna E, Binevski Petr V, Chesnokova Natalia B, Shekhter Anatoly B, Klyachko Natalia L, Kabanov Alexander V
Chemistry Faculty, M.V. Lomonosov Moscow State University, Moscow 119991, Russia.
Helmholtz Institute for Eye Disease, Moscow 105062, Russia.
Oxid Med Cell Longev. 2015;2015:5194239. doi: 10.1155/2016/5194239. Epub 2015 Dec 1.
Use of antioxidants to mitigate oxidative stress during ocular inflammatory diseases has shown therapeutic potential. This work examines a nanoscale therapeutic modality for the eye on the base of antioxidant enzyme, superoxide dismutase 1 (SOD1), termed "nanozyme." The nanozyme is produced by electrostatic coupling of the SOD1 with a cationic block copolymer, poly(L-lysine)-poly(ethyleneglycol), followed by covalent cross-linking of the complexes with 3,3'-dithiobis(sulfosuccinimidylpropionate) sodium salt. The ability of SOD1 nanozyme as well as the native SOD1 to reduce inflammatory processes in the eye was examined in vivo in rabbits with immunogenic uveitis. Results suggested that topical instillations of both enzyme forms demonstrated anti-inflammatory activity; however, the nanozyme was much more effective compared to the free enzyme in decreasing uveitis manifestations. In particular, we noted statistically significant differences in such inflammatory signs in the eye as the intensities of corneal and iris edema, hyperemia of conjunctiva, lens opacity, fibrin clots, and the protein content in aqueous humor. Clinical findings were confirmed by histological data. Thus, SOD1-containing nanozyme is potentially useful therapeutic agent for the treatment of ocular inflammatory disorders.
使用抗氧化剂来减轻眼部炎症性疾病期间的氧化应激已显示出治疗潜力。这项工作研究了一种基于抗氧化酶超氧化物歧化酶1（SOD1）的眼部纳米级治疗方式，即“纳米酶”。纳米酶是通过将SOD1与阳离子嵌段共聚物聚（L-赖氨酸）-聚（乙二醇）进行静电偶联，然后将复合物与3,3'-二硫代双（磺基琥珀酰亚胺丙酸酯）钠盐进行共价交联而产生的。在患有免疫原性葡萄膜炎的兔子体内研究了SOD1纳米酶以及天然SOD1减少眼部炎症过程的能力。结果表明，两种酶形式的局部滴注均显示出抗炎活性；然而，与游离酶相比，纳米酶在减轻葡萄膜炎表现方面更为有效。特别是，我们注意到眼部的此类炎症体征，如角膜和虹膜水肿的强度、结膜充血、晶状体混浊、纤维蛋白凝块以及房水中的蛋白质含量，存在统计学上的显著差异。组织学数据证实了临床发现。因此，含SOD1的纳米酶是治疗眼部炎症性疾病的潜在有用治疗剂。
