Angiopep-2 modified PEGylated 2-methoxyestradiol micelles to treat the PC12 cells with oxygen-glucose deprivation/reoxygenation
Angiopep-2 modified PEGylated 2-methoxyestradiol micelles to treat the PC12 cells with oxygen-glucose deprivation/reoxygenation
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Angiopep-2 修饰的聚乙二醇化 2-甲氧基雌二醇胶束通过氧-葡萄糖剥夺/复氧处理 PC12 细胞
DOI：
10.1016/j.colsurfb.2018.08.009
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发表时间：
2018-11-01
影响因子：
5.8
通讯作者：
Guo, Shengrong
中科院分区：
文献类型：
--
作者：
Hu, Lijun;Wang, Yun;Guo, Shengrong
2-甲氧基乙烯醇（2 ME 2）作为微管和缺氧诱导因子-1（HIP-1）的抑制剂，可用于治疗脑缺血再灌注（I/R）损伤。然而，其差的水溶性损害了其作为神经保护剂的功效。本文中，我们合成了PEG化2 ME 2和angiopep-2封端的PEG化2 ME 2，并通过乳液-溶剂蒸发法制备了含有游离2 ME 2的angiopep-2修饰的PEG化2 ME 2胶束（ANG-PEG-2 ME 2/2 ME 2）。采用PC 12细胞缺氧/复氧（OGD/R）损伤模型，观察胶束对PC 12细胞缺血-复氧损伤的影响。与游离2 ME 2相比，胶束显著增加细胞活力，抑制活性氧（ROS）的产生和细胞凋亡的PC 12细胞OGD 0.5和4 h，然后24 h复氧。因此，angiopep-2修饰的2 ME 2胶束能够有效减轻OGD/R对PC 12细胞的损伤。
2-Methoxyestradiol (2ME2), as a microtubule and hypoxia-inducible factor-1 (HIP-1) inhibitor, can be used to treat cerebral ischemia-reperfusion (I/R) injury. However, its poor water solubility compromises its efficacy as a neuroprotectant. Herein, we synthesized PEGylated 2ME2 and angiopep-2 capped PEGylated 2ME2 and fabricated angiopep-2 modified PEGylated 2ME2 micelles containing free 2ME2 (ANG-PEG-2ME2/2ME2) via emulsion-solvent evaporation method. The effect of the micelles on ischemia-reoxygenation injury was evaluated by oxygen-glucose deprivation/reoxygenation (OGD/R) models with different degrees of PC12 cell damage. In comparison with free 2ME2, the micelles significantly increased the cell viability, inhibited reactive oxygen species (ROS) generation and apoptosis for PC12 cells with 0.5 and 4 h OGD followed by 24 h reoxygenation. Taken together, the angiopep-2 modified 2ME2-loaded micelles could effectively reduce the injury of PC12 cells induced by OGD/R.