摘要
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 determine the cytotoxicity and apoptosis induced by iron oxide nanoparticles（IONPs） with different surface modifications. Methods： The cytotoxicity of PEG-IONP,Amine-IONP and IONP on U87 cells were investigated by CCK-8 assay. The effects of three IONPs with different surface modifications on tumorigenicity of U87 cells were assessed by soft agar cloning method. Early and late apoptosis induced by these IONPs were investigated by Annexin V/PI double dye flow cytometry. Results： All three IONPs inhibited U87 cell proliferation and the colony formation in soft agar in a concentration-dependent manner. When the concentration was higher than 50 μg·m L^-1,all the three iron oxide nanoparticles inhibited U87 cell proliferation in the following order Amine-IONP PEG-IONP IONP. The ability of Amine-IONP inducing apoptosis was significantly higher than those of IONP and PEG-IONP at 10,50 and 200 μg·m L^-1. At 50 μg·m L^-1,the ability of PEG-IONP inducing apoptosis was significantly higher than that of IONP. Furthermore,results of early and late apoptosis demonstrated that IONP and Amine-IONP showed a concentration-dependent manner in inducing apoptosis.Conclusion： Different surface modifications of iron oxide nanoparticles are closely associated with their cytotoxic effects in U87 cells. The toxic effect of positive charged Amine-IONP is significantly more potent than those of PEG-IONP and IONP. PEG-IONP shows an advantage in inhibiting colony formation.
作者
淡墨
赵继云
齐乃松
赵华琛
文海若
张琳
刘丽
DAN Mo ZHAO Ji-yun QI Nai-song ZHAO Hua-chen WEN Hai-ruo ZHANG Lin LIU Li(National Center for Safety Evaluation of Drugs, National Institute for Food and Drug Control, Key Laboratory of Beijing for Nonclinical Safety Evaluation Research of Drugs, Beijing 100176, China)
出处
《中国新药杂志》
CAS
CSCD
北大核心
2016年第24期2887-2892,共6页
Chinese Journal of New Drugs
