二肉豆蔻酰磷脂酰胆碱修饰的氧化铁纳米粒子在PC-12细胞内的分布

Cellular Distribution of 1,2-dimyristoyl-sn-glycero-3-phosphocholine Modified Iron Oxide Nanoparticles

有机物包覆的超顺磁性氧化铁纳米粒子(Superparamagnetic iron oxide nanoparticles,SPIONs)因具有良好的水溶性和生物相容性而被越来越多地用作生物医学研究的工具。采用简便的高温热分解法合成聚乙二醇(Polyethylene glycol,PEG)和聚乙烯亚胺(Polyethyleneimine,PEI)修饰的超顺磁性氧化铁纳米粒子(PEG/PEI-SPIONs),再在其表面通过氢键相互作用接枝二肉豆蔻酰磷脂酰胆碱(1, 2-dimyristoyl-sn-glycero-3-phosphocholine, DMPC),成功制备了DMPC-SPIONs。由热重结果分析可知DMPC的接枝率约为31.7%(质量分数)。将PEG/PEI-SPIONs和DMPC-SPIONs分别与PC-12细胞孵化,对孵化后的细胞进行表征和分析发现,大量的DMPC-SPIONs进入了细胞,而PEG/PEI-SPIONs进入细胞内的量较少。这表明DMPC对于氧化铁纳米粒子进入细胞起到关键作用。通过透射电镜观察与DMPC-SPIONs孵化的PC-12细胞发现,氧化铁纳米粒子密集分布于溶酶体、线粒体、内质网和细胞核膜表面,另外,也有一部分DMPC-SPIONs分布在细胞膜上的纤毛附近,并观察到细胞膜对纳米粒子的内吞现象。DMPC-SPIONs良好的膜透过性及在胞内细胞器的密集分布使其在磁热疗、磁共振成像、药物输运等生物医学领域具有广阔的应用前景。

Superparamagnetic iron oxide nanoparticles(SPIONs)coated with organics have been increasingly used in biomedical research in recent years because of their good aqueous dispersibility and biocompatibility,which is essential for nanoparticles to enter cells.SPIONs coated with polyethylene glycol(PEG)and polyethyleneimine(PEI)(PEG/PEI-SPIONs)were synthesized by high temperature thermal decomposition method,then PEG/PEI-SPIONs were modified with 1,2-dimyristoyl-sn-glycero-3-phosphocholine(DMPC)by hydrogen bonding interactions to obtain DMPC-SPIONs,and thermogravimetric analysis showed that the mass fraction of DMPC on the surface of SPIONs was 31.7wt%.The research on the uptake of PEG/PEI-SPIONs and DMPC-SPIONs by PC-12 cells showed that much more DMPC-SPIONs entered the cells,whereas relatively fewer PEG/PEI-SPIONs were observed in the cells.The results showed that DMPC played an important role in increasing the entry of SPIONs into cells.DMPC-SPIONs were densely distributed in the lysosomes,mitochondria,endoplasmic reticulum and around the nuclei in PC-12 cells.Some DMPC-SPIONs remained in the vicinity of cilia.The endocytosis process of DMPC-SPIONs was observed.DMPC-SPIONs have great potential to be used as hyperthermia agents,MRI contrast agents and drug transportation carriers.