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目的:研究不同表面修饰的纳米氧化铁颗粒(iron oxide nanoparticles,IONPs)对胶质瘤细胞的毒性及其诱导凋亡的差异。方法:首先测定聚乙二醇表面修饰的氧化铁纳米颗粒(PEG-IONP)、氨基表面修饰的氧化铁纳米颗粒(Amine-IONP)和IONP对U87细胞生长的影响。然后利用软琼脂克隆的方法来研究3种IONPs对U87致瘤性的影响。最后用Annexin V/PI双染流式细胞术测定其引起细胞早晚期凋亡的差异。结果:3种IONPs均可抑制U87的增殖和U87软克隆琼脂的形成,并呈明显剂量依赖性。当孵育浓度>50μg·m L~(-1)时,U87生长抑制从大到小排序分别为Amine-IONP>PEG-IONP>IONP。Amine-IONP诱导U87细胞凋亡的能力在低、中和高3个剂量都显著性高于IONP和PEG-IONP;PEG-IONP在中剂量诱导凋亡显著性高于IONP。IONP和Amine-IONP在诱导早晚凋亡上都为剂量正相关。结论:纳米氧化铁颗粒对U87的抑制杀伤作用与其表面修饰密切相关。Amine-IONP抑制细胞生长和诱导凋亡杀伤细胞的能力最强。PEG-IONP在抑制胶质瘤成瘤方面显示出一定的优势。
OBJECTIVE: To study the toxicity of different surface-modified iron oxide nanoparticles (IONPs) to glioma cells and their differences in apoptosis induction. Methods: Firstly, the effects of PEG-IONP, Amine-IONP and IONP on the growth of U87 cells were determined. Then soft agar cloning method to study the three IONPs on U87 tumorigenicity. Finally, Annexin V / PI double staining flow cytometry was used to determine the difference of early and late cell apoptosis. Results: All three IONPs inhibited the proliferation of U87 and the formation of U87 soft-clone agar in a dose-dependent manner. When the incubation concentration was> 50μg · m L -1, the order of inhibition of U87 growth was Amine-IONP> PEG-IONP> IONP. The ability of Amine-IONP to induce apoptosis of U87 cells was significantly higher than that of IONP and PEG-IONP at low, medium and high doses, while PEG-IONP was significantly higher than IONP at middle dose. Both IONP and Amine-IONP were dose-related in inducing early and late apoptosis. Conclusion: The inhibitory effect of nano-iron oxide particles on U87 is closely related to its surface modification. Amine-IONP inhibits cell growth and induces apoptosis with the strongest ability to kill cells. PEG-IONP shows some advantages in inhibiting glioma tumorigenesis.