Superparamagnetic Iron Oxide Nanoparticles with Rigid Cross-linked Polyethylene Glycol Fumarate Coating for Application in Imaging and Drug Delivery
Superparamagnetic Iron Oxide Nanoparticles with Rigid Cross-linked Polyethylene Glycol Fumarate Coating for Application in Imaging and Drug Delivery
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DOI：
10.1021/jp900798r
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发表时间：
2009-05-14
影响因子：
3.7
通讯作者：
Haefeli, Urs O.
中科院分区：
文献类型：
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作者：
Mahmoudi, Morteza;Simchi, Abdolreza;Haefeli, Urs O.
具有适当表面涂层的超顺磁性氧化铁纳米颗粒越来越多地被用于临床应用，如热疗、药物输送、磁共振成像、转染法和细胞/蛋白质分离。要提高磁性纳米颗粒的适用性，必须克服两个主要问题。首先，当药物包裹在颗粒表面时，它的很大一部分在注射时迅速释放(爆裂效应)。因此，在例如磁性药物靶向之后，只有少量的药物到达特定的位置。其次，一旦表面衍生的纳米颗粒进入细胞内部，涂层很可能被消化，使裸露的颗粒暴露在其他细胞成分和细胞器中，从而潜在地影响细胞的整体完整性。为了克服这两个缺点，我们合成了聚乙二醇-富马酸共聚物(PEGF)包覆的氧化铁纳米粒子。由于磁性纳米粒子的分散性好，所获得的材料具有高度的稳定性和易于处理的特点。通过四甲基偶氮唑盐(3-(4，5-dimethylthiazol-2-yl)-2，5-diphenyltetrazolium)分析，即使是非常高浓度的新型磁性纳米颗粒也被发现是生物相容的。为了研究包衣是否可以减少猝发效应，通过加入抗癌药物他莫昔芬来制备纳米颗粒。与未交联的三苯氧胺纳米粒相比，交联的PEGF包衣使猝发效应率降低了21%。我们的结果表明，以交联不饱和脂肪族聚酯为涂层的纳米颗粒在开发药物和基因传递应用的新型载体方面具有潜在的应用价值。
Superparamagnetic iron oxide nanoparticles with proper surface coatings are increasingly being evaluated for clinical applications such as hyperthermia, drug delivery, magnetic resonance imaging, transfection, and cell/protein separation. To enhance the applicability of magnetic nanoparticles, two main problems must be overcome. First, as the drug coats the particle surface, a significant portion of it is quickly released upon injection (burst effect). Therefore, only small amounts of the drug reach the specific site after, for example, magnetic drug targeting. Second, once the surface-derivatized nanoparticles are inside the cells, the coating is likely digested, leaving the bare particles exposed to other cellular components and organelles, thereby potentially influencing the overall integrity of the cells. To overcome these two shortcomings, iron oxide nanoparticles with cross-linked poly (ethylene glycol)-co-fumarate (PEGF) coating were synthesized. The obtained material was highly stable and easy to handle due to the well-dispersed magnetic nanoparticles. Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, even very high concentrations of the novel magnetic nanoparticles were found to be biocompatible. To investigate if the coating could reduce the burst effect, nanoparticles were prepared by incorporating the anticancer drug tamoxifen. The cross-linked PEGF coating reduced the burst effect rate by 21% in comparison with the noncross-linked tamoxifen nanoparticles. Our results suggest that nanoparticles with coatings based on crosslinked unsaturated aliphatic polyesters are potentially useful to develop novel carriers for drug and gene delivery applications.