Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
Eur J Pharm Sci. 2013 Sep 27;50(1):130-8. doi: 10.1016/j.ejps.2013.04.004. Epub 2013 Apr 17.
Superparamagnetic iron oxide nanoparticles (SPIONs) show a great promise for a wide specter of bioapplications, due to their characteristic magnetic properties exhibited only in the presence of magnetic field. Their advantages in the fields of magnetic drug targeting and imaging are well established and their safety is assumed, since iron oxide nanoparticles have already been approved for in vivo application, however, according to many literature reports the bare metal oxide nanoparticles may cause toxic effects on treated cells. Therefore, it is reasonable to prevent the direct interactions between metal oxide core and surrounding environment. In the current research ricinoleic acid coated maghemite nanoparticles were successfully synthesized, characterized and incorporated in the polymeric matrix, resulting in nanosized magnetic polymeric particles. The carrier system was shown to exhibit superparamagnetic properties and was therefore responsive towards external magnetic field. Bioevaluation using T47-D breast cancer cells confirmed internalization of magnetic polymeric nanoparticles (MNPs) and their intracellular localization in various subcellular compartments, depending on presence/absence of external magnetic field. However, the number of internalized MNPs observed by fluorescent and transmission electron microscopy was relatively low, making such way of targeting effective only for delivery of highly potent drugs. The scanning electron microscopy of treated cells revealed that MNPs influenced the cell adhesion, when external magnetic field was applied, and that treatment resulted in damaged apical plasma membrane right after exposure to the magnetic carrier. On the other hand, MNPs showed only reversibly reduced cellular metabolic activity in concentrations up to 200 μg/ml and, in the tested concentration the cell cycle distribution was within the normal range, indicating safety of the established magnetic carrier system for the treated cells.
超顺磁氧化铁纳米颗粒 (SPIONs) 由于其仅在磁场存在下表现出的特征磁性,在广泛的生物应用中具有巨大的应用前景。它们在磁性药物靶向和成像领域的优势已经得到充分证实,并且由于氧化铁纳米颗粒已经被批准用于体内应用,因此其安全性也得到了假设,然而,根据许多文献报道,裸露的金属氧化物纳米颗粒可能对处理过的细胞产生毒性作用。因此,防止金属氧化物核心与周围环境直接相互作用是合理的。在当前的研究中,成功合成、表征并将蓖麻酸包覆的磁赤铁矿纳米颗粒掺入聚合物基质中,得到了纳米级磁性聚合物颗粒。该载体系统表现出超顺磁性,因此对外界磁场有响应。使用 T47-D 乳腺癌细胞进行的生物评估证实了磁性聚合物纳米颗粒 (MNP) 的内化及其在各种亚细胞隔室中的细胞内定位,这取决于是否存在外部磁场。然而,荧光和透射电子显微镜观察到的内化 MNP 的数量相对较少,使得这种靶向方式仅对输送高活性药物有效。处理过的细胞的扫描电子显微镜显示,当施加外部磁场时,MNP 会影响细胞的黏附性,并且在暴露于磁性载体后,处理会导致顶端质膜受损。另一方面,MNP 在高达 200μg/ml 的浓度下仅表现出可还原的细胞代谢活性降低,并且在测试浓度下细胞周期分布在正常范围内,表明所建立的磁性载体系统对处理过的细胞是安全的。
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