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负载芝麻酚的硬脂酸-壳聚糖纳米胶束通过NF-κB信号通路减轻脊髓运动神经元中氧化应激刺激的细胞凋亡和促炎细胞因子的诱导。

Sesamol-loaded stearic acid-chitosan nanomicelles mitigate the oxidative stress-stimulated apoptosis and induction of pro-inflammatory cytokines in motor neuronal of the spinal cord through NF-ĸB signaling pathway.

作者信息

Wang Ning, Yu Hai, Song Qian, Mao Ping, Li Kuo, Bao Gang

机构信息

Department of Neurosurgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

Department of Neurosurgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.

出版信息

Int J Biol Macromol. 2021 Sep 1;186:23-32. doi: 10.1016/j.ijbiomac.2021.06.171. Epub 2021 Jun 29.

Abstract

As natural potential antioxidants suffer from low cellular uptake, the development of drug-loaded nanoplatforms may provide useful information about the treatment of spinal cord injury (SCI). In the present study, sesamol (SM)-loaded stearic acid (SA) -chitosan (CS) nanomicelles were fabricated and well-characterized. Afterwards, the neuroprotective effects of SM@SA-CS nanomicelles against lipopolysaccharide (LPS)-induced oxidative stress in NSC-34 cells was assessed by different cellular and molecular pathways. It was deduced that the size of synthesized SM@SA-CS was in the range of 10-20 nm and the hydrodynamic radii of SA-CA and SM@SA-CA nanomicelles were 53.12 ± 6.21 nm and 59.12 ± 7.31 nm, respectively. Furthermore, SM@SA-CS nanomicelles displayed a sustained drug release at physiological pH, potential dissolution rate and stability even up to 15 days. Cellular assay showed that SM@SA-CS nanomicelles co-incubation with LPS for 24 h in comparison with free drug remarkably regulated cell survival, membrane leakage, generation of ROS, activity of non-enzymatic and enzymatic antioxidant systems, and apoptotic and inflammatory signaling pathway through NF-ĸB signaling pathway. These data indicated that SM@SA-CS nanomicelles can be developed as a promising platform for the mitigation of oxidative stress-mediated apoptosis in neural cells.

摘要

由于天然潜在抗氧化剂存在细胞摄取率低的问题,载药纳米平台的开发可能为脊髓损伤(SCI)的治疗提供有用信息。在本研究中,制备了负载芝麻酚(SM)的硬脂酸(SA)-壳聚糖(CS)纳米胶束并对其进行了充分表征。随后,通过不同的细胞和分子途径评估了SM@SA-CS纳米胶束对脂多糖(LPS)诱导的NSC-34细胞氧化应激的神经保护作用。推断合成的SM@SA-CS的尺寸在10-20nm范围内,SA-CA和SM@SA-CA纳米胶束的流体动力学半径分别为53.12±6.21nm和59.12±7.31nm。此外,SM@SA-CS纳米胶束在生理pH值下显示出持续的药物释放、潜在的溶解速率和稳定性,甚至长达15天。细胞试验表明,与游离药物相比,SM@SA-CS纳米胶束与LPS共孵育24小时可显著调节细胞存活、膜渗漏、活性氧生成、非酶和酶抗氧化系统活性,以及通过NF-κB信号通路的凋亡和炎症信号通路。这些数据表明,SM@SA-CS纳米胶束可被开发成为减轻神经细胞氧化应激介导的凋亡的有前景的平台。

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