Rescue the retina after the ischemic injury by polymer-mediated intracellular superoxide dismutase delivery.
Rescue the retina after the ischemic injury by polymer-mediated intracellular superoxide dismutase delivery.
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DOI：
10.1016/j.biomaterials.2020.120600
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发表时间：
2020-12
期刊：
影响因子：
14
通讯作者：
Xujiao Zhou;Jia Lv;Gang Li;T. Qian;Hao Jiang;Jianjiang Xu;Yiyun Cheng;Jiaxu Hong
中科院分区：
文献类型：
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作者：
Xujiao Zhou;Jia Lv;Gang Li;T. Qian;Hao Jiang;Jianjiang Xu;Yiyun Cheng;Jiaxu Hong
氧化应激是视网膜缺血的病理生理发生的标志。将抗氧化酶如超氧化物歧化酶（SOD）直接递送到视网膜细胞中为视网膜缺血中氧化应激的下调提供了有希望的选择，然而，有效的细胞内蛋白递送仍然是该应用的主要挑战。在这里，富含硼酸的聚合物被用于体外和体内的SOD的细胞内递送。该聚合物与SOD组装成具有高结合亲和力的均匀纳米颗粒，并将货物蛋白转运到几种细胞系中，保持生物活性和低细胞毒性。我们研究了SOD纳米制剂在视网膜缺血/再灌注（I/R）损伤模型中的眼内生物分布、治疗效果和安全性。玻璃体内注射后，纳米颗粒迅速扩散通过玻璃体，并渗透到视网膜神经节细胞（RGC）。与游离SOD相比，纳米制剂表现出大大增强的治疗功效，减少RGC凋亡并保护视网膜功能。酶促结果证实，SOD纳米制剂减少了眼组织中的丙二醛表达并增加了谷胱甘肽水平，从而下调了氧化应激并防止了RGC损失。总的来说，这项工作提供了一个新的治疗选择视网膜缺血性疾病的直接交付的抗氧化蛋白。
Oxidative stress is a hallmark of the pathophysiogenesis of retinal ischemia. The direct delivery of antioxidant enzymes such as superoxide dismutase (SOD) into retinal cells provides a promising option for the down-regulation of oxidative stress in retinal ischemia, however, efficient intracellular protein delivery remains a major challenge for this application. Here, a boronic acid-rich polymer was used for the intracellular delivery of SOD bothin vitroandin vivo. The polymer assembled with SOD into uniform nanoparticles with high binding affinity, and transported the cargo protein into several cell lines with maintained bioactivity and low cytotoxicity. We investigated the intraocular biodistribution, therapeutic efficacy and safety of the SOD nanoformulation in a retinal ischemia/reperfusion (I/R) injury model. After intravitreal injection, the nanoparticles rapidly diffused through the vitreous and penetrated into retinal ganglion cells (RGCs). Compared to free SOD, the nanoformulation exhibited much enhanced therapeutic efficacy with reduced RGC apoptosis and protected retinal function. Enzymatic results confirmed that the SOD nanoformulation reduced malondialdehyde expression and increased glutathione level in the ocular tissues, and thereby down-regulated oxidative stress and prevented RGC loss. Overall, this work offers a new therapeutic option for the treatment of retinal ischemic disorders by direct delivery of antioxidant proteins.