Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
Biomacromolecules. 2013 Mar 11;14(3):828-33. doi: 10.1021/bm301868f. Epub 2013 Feb 1.
To limit cytotoxicity of anticancer drugs against healthy cells, an appropriate carrier should be synthesized to deliver the drug to the tumor tissue only. A good solution is to anchor a magnetic nanoparticle to the molecule of the drug and to use a properly directed external magnetic field. The synthesis of the conjugate of doxorubicin with magnetic nanoparticles (iron oxide) modified by us resulted in a substantial depression of the aggregation process of the nanoparticles and therefore allowed the correct examination of cytotoxicity of the modified drug. It has been shown, by performing the electrochemical microbalance measurements, that the use of magnetic field guaranteed the efficient delivery of the drug to the desired place. The change in the synthesis procedure led to an increase in the number of DOX molecules attached to one magnetic nanoparticle. The release of the drug took place at pH 5.8 (and below it), which pH characterizes the cancer cells. It has also been found that while the iron oxide magnetic nanoparticles were not cytotoxic toward human urinary bladder carcinoma cells UM-UC-3, the tumor cell sensitivity of the DOX-Np complex was slightly higher in comparison to the identical concentration of doxorubicin alone.
为了限制抗癌药物对健康细胞的细胞毒性,应合成适当的载体将药物仅递送到肿瘤组织。一个好的解决方案是将磁性纳米颗粒锚定到药物分子上,并使用适当定向的外部磁场。我们合成了阿霉素与磁性纳米颗粒(氧化铁)的缀合物,这导致纳米颗粒的聚集过程大大减弱,因此允许对修饰药物的细胞毒性进行正确检查。通过进行电化学微天平测量表明,磁场的使用保证了药物的有效递送到所需位置。合成程序的改变导致附着在一个磁性纳米颗粒上的 DOX 分子数量增加。药物的释放发生在 pH 5.8(和更低),该 pH 值是癌细胞的特征。还发现,虽然氧化铁磁性纳米颗粒对人膀胱癌细胞 UM-UC-3 没有细胞毒性,但与单独的阿霉素相同浓度相比,DOX-Np 复合物对肿瘤细胞的敏感性略高。