不同表面修饰的氧化铁纳米粒子标记2-DG靶向横纹肌肉瘤细胞的比较

Biotargeting rhabdomyosarcoma A-673 cell of 2-DG modified superparamagnetic iron oxide nanoparticles with different surface coating

目的:比较二巯基丁二酸(DMSA)和油酸聚乙二醇(OA_2-PEG)包被的纳米粒子表面标记2-脱氧-D-葡萄糖(2-DG)体外靶向肿瘤细胞的差异。方法:制备和表征γ-Fe_2O_3@DMSA-DG NPs和Fe_3O_4@OA-OA_2-PEG-DG NPs。分别用γ-Fe_2O_3@DMSA-DG NPs、γ-Fe_2O_3@DMSA NPs、Fe_3O_4@OA-OA_2-PEG-DG NPs、Fe_3O_4@OA-OA_2-PEG NPs以及Fe_3O_4@OA-OA_2-PEG-DG NPs+D-葡萄糖(4.5 mg/m L,即竞争性抑制组)孵育横纹肌肉瘤A-673细胞10、30、60、120 min,普鲁士蓝染色及磁共振成像(MRI)检测细胞吸收纳米粒子的情况。结果:DMSA包被的纳米粒子与细胞孵育60 min后,γ-Fe_2O_3@DMSA-DG NPs组和γ-Fe_2O_3@DMSA NPs组细胞大量摄取,并且前者摄取量多于后者;OA_2-PEG修饰的纳米粒子与细胞孵育120 min后,与Fe_3O_4@OA-OA_2-PEG NP组和竞争抑制组相比,Fe_3O_4@OA-OA_2-PEG-DG NPs组细胞内见明显摄取。结论:成功合成γ-Fe_2O_3@DMSA-DG NPs和Fe_3O_4@OA-OA_2-PEG-DG NPs,两者对A-673细胞具有较好的靶向性;相比于DMSA对细胞的高亲和性,PEG在抗非特异性细胞黏附的基础上更好地实现了标记物的特异性识别作用,从而使纳米粒子更精准地定位于肿瘤细胞。

Objective：To compare the tumor cells uptake of superparamagnetic iron oxide nanoparticles （SPIONs）marked with 2-DG and coated with different material（DMSA and OA2-PEG） in vitro.Methods：γ-Fe2O3@DMSA-DG NPs and Fe3O4@OA-OA2-PEG-DG NPs were prepared and their characterizations were tested.A-673 cells were incubated with γ-Fe2O3@DMSA-DG NPs、γ-Fe2O3@DMSA NPs and Fe3O4@OA-OA2-PEG-DG NPs, Fe3O4@OA-OA2-PEG NPs and Fe3O4@OA-OA2-PEG-DG NPs in the presence of D-glucose for 10,30,60,120 min.Tumor targeting was studied by Prussian blue staining and magnetic resonance imaging.Results：In nanoparticles coated with DMSA, after incubating with cells 60 min, both γ-Fe2O3@DMSA-DG NPs and γ-Fe2O3@DMSA NPs were uptaked by cells abundantly ,the former was more significantly than the latter.In nanoparticles coated with OA2-PEG,only after 120 min incubating with cells,compared with Fe3O4@OA-OA2-PEG NPs, there was significant uptake of Fe3O4@OA-OA2-PEG-DG NPs by A-673 cells, which was inhibited by glucose.Conclusion：γ-Fe2O3@DMSA-DG NPs and Fe3O4@OA-OA2-PEG-DG NPs were prepared successfully, both of them can target the glut-expressing of A-673 cells well.Compared with DMSAs good affinity to cell, PEG can resist nonspecific cell adhesion and realize specific identification for the receptors better, making Fe3O4@OA-OA2-PEG-DG NPs target tumor cell more precisely.