Metin Esra, Mutlu Pelin, Gündüz Ufuk
Middle East Technical University, Department of Biotechnology, Ankara, Turkey.
Middle East Technical University, Central Laboratory, Molecular Biology and Biotechnology R&D, Ankara, Turkey.
Anticancer Agents Med Chem. 2018;18(8):1138-1147. doi: 10.2174/1871520618666180313154724.
Although conventional chemotherapy is the most common method for cancer treatment, it has several side effects such as neuropathy, alopecia and cardiotoxicity. Since the drugs are given to body systemically, normal cells are also affected, just like cancer cells. However, in recent years, targeted drug delivery has been developed to overcome these drawbacks.
The aim of this study was targeted co-delivery of doxorubicin (Dox) which is an anticancer agent and D-α-Tocopherol polyethylene glycol 1000 succinate (vitamin E TPGS or simply TPGS) to breast cancer cells. For this purpose, Magnetic Nanoparticles (MNPs) were synthesized and coated with Oleic Acid (OA). Coated nanoparticles were encapsulated in Poly Lactic-co-Glycolic Acid (PLGA) and TPGS polymers and loaded with Dox. The Nanoparticles (NPs) were characterized by Fourier Transform Infrared (FTIR) spectroscopy, zetapotential analysis, Dynamic Light Scattering (DLS) analysis, Thermal Gravimetric Analysis (TGA) and Scanning Electron Microscope (SEM) analysis.
The results showed that NPs were spherical, superparamagnetic and in the desired range for use in drug targeting. The targetability of NPs was confirmed. Moreover, TPGS and Dox loading was shown by TGA and FTIR analyses. NPs were internalized by cells and the cytotoxic effect of drug loaded NPs on sensitive (MCF-7) and drug-resistant (MCF-7/Dox) cells were examined. It was seen that the presence of TPGS increased cytotoxicity significantly. TPGS also enhanced drug loading efficiency, release rate, cellular internalization. In MCF- 7/Dox cells, the drug resistance seems to be decreased when Dox is loaded onto TPGS containing NPs.
This magnetic PLGA nanoparticle system is important for new generation targeted chemotherapy and could be used for breast cancer treatment after in vivo tests.
尽管传统化疗是癌症治疗最常用的方法，但它有多种副作用，如神经病变、脱发和心脏毒性。由于药物是全身给药，正常细胞也会像癌细胞一样受到影响。然而，近年来，靶向药物递送技术得以发展以克服这些缺点。
本研究的目的是将抗癌药物阿霉素（Dox）和聚乙二醇1000维生素E琥珀酸酯（维生素E TPGS或简称为TPGS）靶向共递送至乳腺癌细胞。为此，合成了磁性纳米颗粒（MNPs）并用油酸（OA）进行包覆。将包覆后的纳米颗粒封装在聚乳酸-羟基乙酸共聚物（PLGA）和TPGS聚合物中，并负载阿霉素。通过傅里叶变换红外光谱（FTIR）、zeta电位分析、动态光散射（DLS）分析、热重分析（TGA）和扫描电子显微镜（SEM）分析对纳米颗粒（NPs）进行表征。
结果表明，纳米颗粒呈球形，具有超顺磁性，且在用于药物靶向的理想范围内。证实了纳米颗粒的靶向性。此外，通过TGA和FTIR分析显示了TPGS和阿霉素的负载情况。细胞摄取了纳米颗粒，并检测了负载药物的纳米颗粒对敏感细胞（MCF-7）和耐药细胞（MCF-7/Dox）的细胞毒性作用。可以看出，TPGS的存在显著增加了细胞毒性。TPGS还提高了药物负载效率、释放速率和细胞摄取率。在MCF-7/Dox细胞中，当阿霉素负载到含TPGS的纳米颗粒上时，耐药性似乎有所降低。
这种磁性PLGA纳米颗粒系统对新一代靶向化疗具有重要意义，经体内试验后可用于乳腺癌治疗。
