Erdem M, Yalcin S, Gunduz U
1 Department of Biology, Middle East Technical University, Ankara, Turkey.
2 Department of Food Engineering, Ahi Evran University, Kirşehir, Turkey.
Hum Exp Toxicol. 2017 Aug;36(8):833-845. doi: 10.1177/0960327116672910. Epub 2016 Oct 10.
Conventional chemotherapy is the most valid method to cope with cancer; however, it has serious drawbacks such as decrease in production of blood cells or inflammation of the lining of the digestive tract. These side effects occur since generally the drugs used in chemotherapy are distributed evenly within the body of the patient and cannot distinguish the cancer cells from the healthy ones. In this study, folic acid (FA)-conjugated, polyethylene-coated magnetic nanoparticles (FA-MNPs), and doxorubicin (Dox)-loaded formulation (Dox-FA-MNPs) were prepared. The cytotoxicity of these nanoparticles on HeLa and Dox-resistant HeLa cells was investigated. Magnetic nanoparticles (MNPs), polyethylene glycol (PEG)-coated MNPs (PEG-MNPs), and FA-MNPs were successfully synthesized and characterized by several methods. Dox loading of FA-MNPs and release profile of Dox from the nanoparticles were studied. Cytotoxic effects of FA-MNPs and Dox-FA-MNPs on HeLa cells were analyzed. MNPs, PEG-MNPs, and FA-MNPs all had small sizes and supermagnetic behavior. High amounts of Dox could be loded onto the nanoparticles (290 μgmL). In 24 h, 15.7% of Dox was released from the Dox-FA-MNPs. The release was increased in acidic conditions (pH 4.1). Internalization studies showed that FA-MNPs and Dox-FA-MNPs were taken up efficiently by HeLa cells. The investigation of cytotoxicity of the particles indicated that 38-500 μgmL Dox-FA-MNPs significantly decreased the proliferation of HeLa cells compared to FA-MNPs. Due to their size, magnetic properties, internalization, drug release, and cytotoxicity characteristics, the MNPs prepared in this study may have potential application as a drug delivery system in cancer chemotherapy.
传统化疗是应对癌症最有效的方法;然而,它有严重的缺点,如血细胞生成减少或消化道内膜炎症。这些副作用的出现是因为化疗中使用的药物通常在患者体内均匀分布,无法区分癌细胞和健康细胞。在本研究中,制备了叶酸(FA)共轭的、聚乙二醇包覆的磁性纳米颗粒(FA-MNPs)以及负载阿霉素(Dox)的制剂(Dox-FA-MNPs)。研究了这些纳米颗粒对HeLa细胞和耐Dox的HeLa细胞的细胞毒性。成功合成了磁性纳米颗粒(MNPs)、聚乙二醇(PEG)包覆的MNPs(PEG-MNPs)和FA-MNPs,并通过多种方法对其进行了表征。研究了FA-MNPs的Dox负载量以及Dox从纳米颗粒中的释放曲线。分析了FA-MNPs和Dox-FA-MNPs对HeLa细胞的细胞毒性作用。MNPs、PEG-MNPs和FA-MNPs均具有小尺寸和超顺磁性行为。大量的Dox可以负载到纳米颗粒上(290μg/mL)。在24小时内,15.7%的Dox从Dox-FA-MNPs中释放出来。在酸性条件(pH 4.1)下释放增加。内化研究表明,HeLa细胞能有效摄取FA-MNPs和Dox-FA-MNPs。颗粒细胞毒性研究表明,与FA-MNPs相比,38 - 500μg/mL的Dox-FA-MNPs显著降低了HeLa细胞的增殖。由于其尺寸、磁性、内化、药物释放和细胞毒性特性,本研究制备的MNPs在癌症化疗中作为药物递送系统可能具有潜在应用。