Dual-targeting and specific delivery of tamoxifen to cancer cells by modified magnetic nanoparticles using hyaluronic acid and folic acid

Mostafa Heidari Majd
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引用次数: 2

Abstract

Tamoxifen (TMX) which serves as the best clinical option for the treatment of breast cancer may trigger major dose-dependent side effects due to its poor solubility. Therefore, the use of lower TMX doses utilizing nano-enabled drug delivery systems offers multiple benefits to improving drug specified concentration, safety, and long-term release. In this study, we synthesized targeted magnetic nanoparticles (MNPs) containing folic acid (FA) and hyaluronic acid (HA) to improve drug delivery of TMX. After investigations utilizing Fourier-transform infrared spectroscopy and field emission scanning electron microscope, we found that the surface of MNPs was well modified with targeting agents, and the size of the Fe3O4-DPN-HA-FA NPs was determined at ∼153 (±3.3) nm. Furthermore, the release of 81% TMX after 120 h indicated that there was a controlled pattern of drug release from the modified MNPs. Besides that, the MTT assay revealed that the viability of MDA-MB-231 cell lines after 48 h and 72 h of treatment is dependent on the time and concentration of Fe3O4-DPN-HA-FA-TMX NPs. Finally, real-time polymerase chain reaction demonstrated that Fe3O4-DPN-HA-FA-TMX NPs could upregulate the expression of Bak1 genes and downregulated the expression of Bclx genes during 24 h treatment. All data confirmed that the presence of HA and FA on the surface of nanocarriers and the active targeting employing the nanocarriers can be a useful step to obliterate the breast cancer cells.
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利用透明质酸和叶酸修饰的磁性纳米颗粒对癌细胞的双靶向和特异性递送他莫昔芬
他莫昔芬(TMX)作为治疗乳腺癌的最佳临床选择,由于其溶解度差,可能会引发严重的剂量依赖性副作用。因此,利用纳米给药系统使用较低剂量的TMX,在提高药物指定浓度、安全性和长期释放方面具有多种益处。在这项研究中,我们合成了含有叶酸(FA)和透明质酸(HA)的靶向磁性纳米颗粒(MNPs),以改善TMX的药物传递。通过傅里叶变换红外光谱和场发射扫描电镜的研究,我们发现MNPs的表面被靶向剂很好地修饰,Fe3O4-DPN-HA-FA NPs的尺寸在~ 153(±3.3)nm处被确定。此外,120 h后,81%的TMX释放表明修饰的MNPs具有控制的药物释放模式。此外,MTT实验显示,MDA-MB-231细胞株在处理48 h和72 h后的活力与Fe3O4-DPN-HA-FA-TMX NPs的时间和浓度有关。最后,实时聚合酶链反应表明,在处理24 h时,Fe3O4-DPN-HA-FA-TMX NPs可以上调Bak1基因的表达,下调Bclx基因的表达。所有数据都证实了HA和FA在纳米载体表面的存在以及利用纳米载体的主动靶向可以是消灭乳腺癌细胞的有用步骤。
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