Robust neuroprotective effects of intranasally delivered iNOS siRNA encapsulated in gelatin nanoparticles in the postischemic brain
Robust neuroprotective effects of intranasally delivered iNOS siRNA encapsulated in gelatin nanoparticles in the postischemic brain
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DOI：
10.1016/j.nano.2016.01.002
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发表时间：
2016-07-01
影响因子：
5.4
通讯作者：
Lee, Ja-Kyeong
中科院分区：
文献类型：
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作者：
Kim, Il-Doo;Sawicki, Elizabeth;Lee, Ja-Kyeong
封装在与 0.0667% 戊二醛 (GA) 交联的明胶纳米颗粒（GNP；直径 188.0 +/- 60.9 nm）后，在缺血后大鼠脑中研究了鼻内 iNOS siRNA 递送的治疗效果。输注后 1 小时，在许多大脑区域的细胞外和细胞内区室中发现了鼻内递送的 GNP，包括嗅球、大脑皮层和纹状体，并且持续检测到数天。当大脑中动脉闭塞（MCAO）60分钟后2天，当MCAO后6小时递送iNOS siRNA/GNP时，梗塞体积被显着抑制（最大减少至42.1+/-2.6%）。此外，这种保护作用还表现为神经和行为缺陷的减少，并持续两周。 iNOS siRNA/GNP 的治疗效力比裸 siRNA 明显更大且持续时间更长，并且 iNOS siRNA/GNP 延长且有效的 iNOS 是产生强大神经保护作用的原因。 (C) 2016 Elsevier Inc. 保留所有权利。
The therapeutic efficacy of intranasal iNOS siRNA delivery was investigated in the postischemic rat brain after encapsulating on in gelatin nanoparticles (GNPs; diameter 188.0 +/- 60.9 nm) cross-linked with 0.0667% glutaraldehyde (GA). Intranasally delivered GNPs were found in extracellular and intracellular compartments of many brain regions, including the olfactory bulb, cerebral cortex, and striatum at 1 hour after infusion and continued to be detected for days. Infarct volumes were markedly suppressed (maximal reduction to 42.1 +/- 2.6%) at 2 days after 60 minutes of middle cerebral artery occlusion (MCAO) when iNOS siRNA/GNPs were delivered at 6 hours post-MCAO. In addition, this protective effect was manifested by reductions in neurological and behavioral deficits that were sustained for 2 weeks. Therapeutic potency of iNOS siRNA/GNPs was significantly greater and sustained longer than that of bare siRNA and prolonged and efficient iNOS by iNOS siRNA/GNP is responsible for the robust neuroprotective effect. (C) 2016 Elsevier Inc. All rights reserved.