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Angiopep-2 modified PEGylated 2-methoxyestradiol micelles to treat the PC12 cells with oxygen-glucose deprivation/reoxygenation.
Colloids and Surfaces. B, Biointerfaces 2018 November 2
2-Methoxyestradiol (2ME2), as a microtubule and hypoxia-inducible factor-1 (HIF-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.
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