不同表面修饰的氧化铁纳米颗粒诱导胶质瘤细胞自噬和凋亡的差异及自噬的调控作用

目的：研究不同表面修饰的氧化铁纳米颗粒（iron oxide nanoparticles，IONPs）诱导胶质瘤细胞自噬和凋亡抑制杀伤作用的差异及自噬对凋亡的调控作用。方法：首先测定抑制自噬情况下，聚乙二醇表面修饰的氧化铁纳米颗粒（PEG-IONPs）、氨基表面修饰的氧化铁纳米颗粒（Amine-IONPs）和IONPs对人脑胶质瘤细胞（U87）生长的影响；然后利用高内涵的方法来评价3种IONPs对诱导U87自噬能力的影响；最后用流式细胞术测定其引起细胞早晚期凋亡的差异，并同时评价诱导和抑制自噬对凋亡的影响。结果：3种IONPs在10、50和200 μg·mL^-1浓度时均可抑制U87的增殖，并呈明显剂量依赖性。Amine-IONPs诱导U87凋亡的能力显著性高于IONPs和PEG-IONPs。3种IONPs均可以显著性诱导U87产生自噬。抑制自噬可以显著性增强低剂量IONPs，特别是Amine-IONPs诱导的凋亡；然而抑制自噬反而降低高剂量IONPs和Amine-IONPs诱导的细胞凋亡。结论：不同表面修饰的IONPs诱导U87产生自噬和凋亡作用与其表面修饰密切相关。Amine-IONPs诱导的自噬在低高剂量显示出双向调节作用。

Objective:To study the autophagy and the inhibition of apoptosis in glioma cells(U87) induced by iron oxide nanoparticles(IONPs) with different surface modifications and the regulation by autophagy.Methods:The effect of PEG-IONPs, Amine-IONPs and IONPs on the growth of human glioma cells(U87) were measured after autophagy inhibition.Then, the effects of three IONPs induced U87 autophagy were evaluated using the high-content method.Finally, the differences of early and late apoptosis induced by flow cytometry were measured, and the effects of induction and inhibition of autophagy on apoptosis were also evaluated.Results:The three IONPs all inhibited the proliferation of U87 in a dose range from 10 μg·mL^-1 to 200 μg·mL^-1 with a dose-dependent manner.The ability of Amine-IONPs inducing apoptosis of U87 was significantly higher than that of IONPs and PEG-IONPs.Inhibition of autophagy can significantly enhance the apoptosis induced by IONPs at low dose IONPs, especially Amine-IONPs.However, inhibition of autophagy reduced apoptosis induced by high-dose IONPs and Amine-IONPs.Conclusion:The autophagy and apoptosis of U87 induced by different surface modifications are closely related to the surface modification.The autophagy induced by Amine-IONPs shows the dual-directional regulation on apoptosis at low and high dose levels.