高等学校化学学报 ›› 2018, Vol. 39 ›› Issue (9): 2071-2079.doi: 10.7503/cjcu20180033

• 高分子化学 • 上一篇    下一篇

过氧化氢敏感的靶向荧光载药纳米粒子的制备及在动脉粥样硬化中的应用

方超1, 朱焓毓1, 刘晔1, 赵外欧2, 李亚鹏1(), 王静媛1   

  1. 1. 吉林大学化学学院, 麦克德尔米德实验室, 长春 130012
    2. 吉林大学第一医院, 长春 130021
  • 收稿日期:2018-01-09 出版日期:2018-09-07 发布日期:2018-03-26
  • 作者简介:

    联系人简介: 李亚鹏, 男, 博士, 教授, 博生生导师, 主要从事医用高分子的相关研究. E-mail: liyapeng@jlu.edu.cn

Synthesis and Characterization of Nanoparticles with Hydrogen Peroxide Sensitivity, Targeting and Fluorscence for Atherosclerosis

FANG Chao1, ZHU Hanyu1, LIU Ye1, ZHAO Waiou2, LI Yapeng1,*(), WANG Jingyuan1   

  1. 1. Alan G. MacDiarmid Institute, College of Chemistry, Jilin University, Changchun 130012, China
    2. The First Hospital of Jilin University, Changchun 130021, China
  • Received:2018-01-09 Online:2018-09-07 Published:2018-03-26
  • Contact: LI Yapeng E-mail:liyapeng@jlu.edu.cn

摘要:

活性氧(ROS)在动脉粥样硬化斑块的形成过程中起着重要作用, 特别是过氧化氢在动脉硬化内皮损伤处有着较高含量, 其可以刺激巨噬细胞表达促炎细胞因子和趋化因子来加剧巨噬细胞的致炎活动. 因此, 开发具有过氧化氢敏感释放的药物, 对于安全有效治疗动脉粥样硬化具有重大意义. 将聚甲基丙烯酸羟乙酯(PHEMA)侧链羟基分别接枝草酰基辛伐他汀(Sim)(降低血脂前药)、 含氧杂六元环的荧光聚乙二醇(FPEG)及巨噬细胞的靶分子ISO-1, 制备了具有过氧化氢敏感型的靶向荧光载药纳米胶束(PHEMA-Sim-FPEG-ISO-1). 该纳米粒子利用过氧化氢敏感可控释药, 能够靶向巨噬细胞, 同时改进传统聚乙二醇仅作亲水链的特点, 合成具有荧光功能的聚乙二醇, 使聚合物无需修饰荧光物质便拥有探针能力, 适于动脉粥样硬化的诊疗. 结果表明, 该水溶性纳米粒子显示出较好的生物相容性、 过氧化氢敏感性及荧光能力, 为发展动脉粥样硬化的诊疗一体的纳米体系提供新材料.

关键词: 两亲纳米粒子, 过氧化氢敏感, 药物释放, 荧光聚合物, 动脉粥样硬化

Abstract:

A multifunctional nanomicelle was designed for atherosclerosis theranostics, which was synthesized by decorating the poly(2-hydroxyethyl methacrylate)(PHEMA) with simvastatin(Sim) prodrug, fluorescent polyethylene glycol(FPEG) and the macrophages targeting molecules(ISO-1). The as-obtained polymer was confirmed by nuclear magnetic resonance(1H NMR), Fourier transform infrared spectroscopy(FTIR) and gel permeation chromatography(GPC). The nanoparticle size and morphology were determined by dynamic light scattering(DLS) and transmission electron microscopy(TEM), which was spherical and with the size of about 100 nm. The MTT assay confirmed the biocompatibility of the nanomicelles. The targeting property was evaluated by cell uptake assay and observed via confocal laser scanning microscopy(CLSM). The results suggest that this multifunctional H2O2-respective targeting nanomicelles could become an effective tool for atherosclerosis therapy.

Key words: Amphiphilic nanoparticles, Hydrogen peroxide sensitivity, Drug release, Fluorescent polymer, Atherosclerosis

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