高等学校化学学报 ›› 2019, Vol. 40 ›› Issue (9): 1998-2004.doi: 10.7503/cjcu20190247

• 物理化学 • 上一篇    下一篇

靶向纳米钻石-甲氨蝶呤药物体系制备及与MCF-7细胞作用

李林1,*(),许鑫汝1,李英奇3,张彩凤1,2   

  1. 1. 太原师范学院化学系, 晋中 030619
    2. 山西省腐植酸工程技术研究中心, 晋中 030619
    3. 山西大学化学化工学院, 太原 030006
  • 收稿日期:2019-04-28 出版日期:2019-09-10 发布日期:2019-08-20
  • 通讯作者: 李林 E-mail:lilin@tynu.edu.cn
  • 基金资助:
    山西省青年科技研究基金(201801D221440);山西省应用基础研究基金(201801D121257);太原师范学院大学生科技创新项目(2018503 CXCY1850)

Preparation of Targeting Nanodiamond-metaminopterone Drug System and Its Interaction with MCF-7 Cells

LI Lin1,*(),XU Xinru1,LI Yingqi3,ZHANG Caifeng1,2   

  1. 1. Department of Chemistry, Taiyuan Normal University, Jinzhong, 030619, China
    2. Humic Acid Engineering and Technology Research Center of Shanxi Province, Jinzhong 030619, China
    3. College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China
  • Received:2019-04-28 Online:2019-09-10 Published:2019-08-20
  • Contact: LI Lin E-mail:lilin@tynu.edu.cn
  • Supported by:
    ? Supported by the Shanxi Youth Science and Technology Research Fund Project, China(201801D221440);the Shanxi Provincial Applied Fundamental Research Fund Project, China(201801D121257);the Taiyuan Normal University College Students Science and Technology Innovation Project, China(No. 2018503 CXCY1850)(2018503 CXCY1850)

摘要:

以羧基化纳米钻石(ND-COOH)为基体, 通过共价键合方法将聚乙二醇二胺(H2N-PEG-NH2)、 叶酸(FA)和缩水甘油(GLY)偶联于ND-COOH表面, 赋予纳米钻石载体较好的水溶分散性和靶向性, 借助氢键和范德华力等作用力负载甲氨蝶呤(MTX), 得到靶向纳米钻石-聚乙二醇二胺-叶酸/缩水甘油/甲氨蝶呤(ND-PEG-FA/GLY/MTX NPF/G/M)纳米药物体系. 采用透射电子显微镜、 X射线能量色散谱、 粒径及电位测试证实已制备NPF/G/M. 体外释药发现NPF/G/M在肿瘤环境(pH=5.5)中的药物释放量为正常生理环境(pH=7.4)中的3倍, 表明其具有良好的药物输送特性. 此外, 利用流式细胞术和MTT毒性测试探究了MCF-7细胞摄取NPF/G/M的机制及动力学特性和细胞毒性, 结果表明NPF/G/M以依赖能量、 温度、 网格蛋白、 小窝蛋白和叶酸受体介导的机制进入细胞, 从而将药物缓慢释放于细胞内, 进而诱导细胞凋亡. 研究结果表明, NPF/G/M可作为一种良好的药物输送体系, 为其应用于乳腺癌的临床治疗提供理论参考.

关键词: 纳米钻石, 聚乙二醇二胺, 叶酸, 缩水甘油, 甲氨蝶呤, 靶向纳米药物

Abstract:

We fabricated a targeted nanodiamond drug system(NPF/G/M) through physical adsorption of methotrexate(MTX) using carboxylated nanodiamonds(ND-COOH) modified with polyethylene glycol diamine(H2N-PEG-NH2), folic acid(FA) and glycidol(GLY) as carriers. The preparation of NPF/G/M was verified by morphological observation, energy dispersive spectroscopy(EDS) of the elemental analysis, zeta potential and particle size. The results showed that NPF/G/M can be effectively released in the tumor site, which is three times than in the physiological environment(pH=7.4). Relying on the high affinity between folate and folate receptors, NPF/G/M was uptaken by tumor cells through energy, temperature, clathrin, caveolin-dependent and folate receptor-mediated endocytosis. Interestingly, toxicity tests showed that NPF/G/M can slowly release the drug into the cells and induce cell apoptosis. The above results indicate that NPF/G/M can be used as a good drug delivery system, which will provide a theoretical reference for clinical application in breast cancer.

Key words: Nanodiamond, Polyethylene glycol diamine, Folic acid, Glycidol, Methotrexate, Targeted nanodrug

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