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负载伊达比星的叶酸共轭磁性纳米颗粒作为乳腺癌的靶向给药系统。

Idarubicin-loaded folic acid conjugated magnetic nanoparticles as a targetable drug delivery system for breast cancer.

作者信息

Gunduz Ufuk, Keskin Tugba, Tansık Gulistan, Mutlu Pelin, Yalcin Serap, Unsoy Gozde, Yakar Arzu, Khodadust Rouhollah, Gunduz Gungor

机构信息

Middle East Technical University, Department of Biological Sciences, Ankara 06800, Turkey; Middle East Technical University, Department of Biotechnology, Ankara 06800, Turkey.

Middle East Technical University, Department of Biological Sciences, Ankara 06800, Turkey.

出版信息

Biomed Pharmacother. 2014 Jul;68(6):729-36. doi: 10.1016/j.biopha.2014.08.013. Epub 2014 Aug 22.

DOI:10.1016/j.biopha.2014.08.013
PMID:25194441
Abstract

Conventional cancer chemotherapies cannot differentiate between healthy and cancer cells, and lead to severe side effects and systemic toxicity. Another major problem is the drug resistance development before or during the treatment. In the last decades, different kinds of controlled drug delivery systems have been developed to overcome these shortcomings. The studies aim targeted drug delivery to tumor site. Magnetic nanoparticles (MNP) are potentially important in cancer treatment since they can be targeted to tumor site by an externally applied magnetic field. In this study, MNPs were synthesized, covered with biocompatible polyethylene glycol (PEG) and conjugated with folic acid. Then, anti-cancer drug idarubicin was loaded onto the nanoparticles. Shape, size, crystal and chemical structures, and magnetic properties of synthesized nanoparticles were characterized. The characterization of synthesized nanoparticles was performed by dynamic light scattering (DLS), Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), scanning electron microscopy (SEM) analyses. Internalization and accumulation of MNPs in MCF-7 cells were illustrated by light and confocal microscopy. Empty MNPs did not have any toxicity in the concentration ranges of 0-500μg/mL on MCF-7 cells, while drug-loaded nanoparticles led to significant toxicity in a concentration-dependent manner. Besides, idarubicin-loaded MNPs exhibited higher toxicity compared to free idarubicin. The results are promising for improvement in cancer chemotherapy.

摘要

传统的癌症化疗方法无法区分健康细胞和癌细胞,会导致严重的副作用和全身毒性。另一个主要问题是在治疗前或治疗期间会产生耐药性。在过去几十年中,人们开发了各种控释给药系统来克服这些缺点。这些研究旨在将药物靶向递送至肿瘤部位。磁性纳米颗粒(MNP)在癌症治疗中具有潜在的重要性,因为它们可以通过外部施加的磁场靶向肿瘤部位。在本研究中,合成了磁性纳米颗粒,用生物相容性聚乙二醇(PEG)包覆,并与叶酸偶联。然后,将抗癌药物伊达比星负载到纳米颗粒上。对合成纳米颗粒的形状、尺寸、晶体和化学结构以及磁性进行了表征。通过动态光散射(DLS)、傅里叶变换红外光谱(FT-IR)、透射电子显微镜(TEM)、扫描电子显微镜(SEM)分析对合成纳米颗粒进行了表征。通过光学显微镜和共聚焦显微镜说明了磁性纳米颗粒在MCF-7细胞中的内化和积累情况。在0-500μg/mL浓度范围内,空白磁性纳米颗粒对MCF-7细胞没有任何毒性,而载药纳米颗粒则以浓度依赖性方式导致显著毒性。此外,与游离伊达比星相比,载伊达比星的磁性纳米颗粒表现出更高的毒性。这些结果为癌症化疗的改进带来了希望。

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