Zein nanoparticles loaded with chloroquine improve functional recovery and attenuate neuroinflammation after spinal cord injury
Zein nanoparticles loaded with chloroquine improve functional recovery and attenuate neuroinflammation after spinal cord injury
复制标题
DOI：
10.1016/j.cej.2022.137882
复制
发表时间：
2022-07
影响因子：
15.1
通讯作者：
Xianghan Chen;Beini Wang;Yuqin Mao;Abdullah Al Mamun;Man Wu;Shuyi Qu;Xie Zhang;Jinjing Zhang
中科院分区：
文献类型：
--
作者：
Xianghan Chen;Beini Wang;Yuqin Mao;Abdullah Al Mamun;Man Wu;Shuyi Qu;Xie Zhang;Jinjing Zhang
炎症是继发性脊髓损伤（SCI）中的关键分子事件。然而，氯喹（CQ）是一种具有显着抗炎作用的抗疟疾药物。玉米醇溶蛋白是一种源自天然植物蛋白的可生物降解生物材料，因其良好的生物相容性和生物降解性而广泛应用于药物缓释载体。在这项研究中，我们研究了负载 CQ 的玉米醇溶蛋白纳米颗粒 (NP) 在 SCI 中的显着影响和潜在分子机制。更重要的是，我们发现 SCI 后局部递送 Zein-CQ NP 可以显着改善功能恢复，抑制神经元凋亡，减轻神经炎症并增强 M2 表型小胶质细胞极化。从机制上讲，我们的研究结果进一步证明，局部给予 Zein-CQ NP 可抑制大鼠 SCI 后 MAPK/NF-κB 信号通路的激活。此外，Zein-CQ NP 减少了促炎因子的释放，并增强了脂多糖 (LPS) 刺激的 BV2 细胞中 M2 表型小胶质细胞的蛋白表达。我们的研究结果表明，Zein-CQ NP 的局部递送对于 SCI 的治疗和管理具有良好的治疗效果。
Inflammation is a pivotal molecular event in secondary spinal cord injury (SCI). However, chloroquine (CQ) is an anti-malarial drug with remarkable anti-inflammatory effects. Zein is a biodegradable biomaterial derived from natural-plant protein and is widely applied in drug sustained-release carriers due to its promising biocompatibility and biodegradability. In this research, we investigated the significant effects and underlying molecular mechanisms of zein nanoparticles (NPs) loaded with CQ in SCI. More importantly, we found that local delivery of Zein-CQ NPs after SCI could significantly improved functional recovery, inhibited neuronal apoptosis, alleviated neuroinflammation and enhanced M2 phenotype microglia polarization. Mechanistically, our findings further demonstrated that local administration of Zein-CQ NPs inhibited activation of the MAPK/NF-κB signaling pathway after SCI in rats. Moreover, Zein-CQ NPs reduced the release of pro-inflammatory factors and augmented the protein expression of M2 phenotype microglia in lipopolysaccharide (LPS)-stimulated BV2 cells. Our findings imply that local delivery of Zein-CQ NPs produces promising therapeutic benefits for the treatment and management of SCI.