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  • CN 31-1691/TQ

可用于电子顺磁共振检测的pH响应载药胶束的制备与体外评价

王兆东 史炉炉 赵红莉 洪亚云 周丽芳 蓝闽波

王兆东, 史炉炉, 赵红莉, 洪亚云, 周丽芳, 蓝闽波. 可用于电子顺磁共振检测的pH响应载药胶束的制备与体外评价[J]. 华东理工大学学报(自然科学版), 2019, 45(6): 910-918. doi: 10.14135/j.cnki.1006-3080.20180725001
引用本文: 王兆东, 史炉炉, 赵红莉, 洪亚云, 周丽芳, 蓝闽波. 可用于电子顺磁共振检测的pH响应载药胶束的制备与体外评价[J]. 华东理工大学学报(自然科学版), 2019, 45(6): 910-918. doi: 10.14135/j.cnki.1006-3080.20180725001
WANG Zhaodong, SHI Lulu, ZHAO Hongli, HONG Yayun, ZHOU Lifang, LAN Minbo. EPR-Detectable and pH-Responsive Drug-Loaded Micelles: Preparation and in vitro Evaluation[J]. Journal of East China University of Science and Technology, 2019, 45(6): 910-918. doi: 10.14135/j.cnki.1006-3080.20180725001
Citation: WANG Zhaodong, SHI Lulu, ZHAO Hongli, HONG Yayun, ZHOU Lifang, LAN Minbo. EPR-Detectable and pH-Responsive Drug-Loaded Micelles: Preparation and in vitro Evaluation[J]. Journal of East China University of Science and Technology, 2019, 45(6): 910-918. doi: 10.14135/j.cnki.1006-3080.20180725001

可用于电子顺磁共振检测的pH响应载药胶束的制备与体外评价

doi: 10.14135/j.cnki.1006-3080.20180725001
基金项目: 上海市科委“科技创新行动计划”(15441904100)
详细信息
    作者简介:

    王兆东(1993-),男,内蒙古巴彦淖尔市人,硕士生,研究方向纳米载药材料。E-mail:490229890@qq.com

    通讯作者:

    蓝闽波,E-mail:minbolan@ecust.edu.cn

  • 中图分类号: TQ317

EPR-Detectable and pH-Responsive Drug-Loaded Micelles: Preparation and in vitro Evaluation

  • 摘要: 基于乙炔聚合反应,以席夫碱作为酸响应基团,合成了含有2,2,6,6-四甲基哌啶氮氧化物(TEMPO)自由基的pH响应聚合物PA-pH-TEMPO,利用核磁共振氢谱(1H-NMR)、傅里叶变换红外光谱(FT-IR)、电子顺磁共振波谱(EPR)等对其分子结构进行了表征;以广谱抗肿瘤药物阿霉素(DOX)为模型药物,通过透析法制得了载DOX的胶束DOX@PA-pH-TEMPO。结果表明,PA-pH-TEMPO在对小鼠成纤维细胞L929和人子宫癌细胞HeLa的毒性测试中,没有明显的细胞毒性;DOX@PA-pH-TEMPO胶束的载药量和包封率分别为2.58%和32.09%,表现出良好的pH响应特性和缓释性能,且对HeLa肿瘤细胞具有较强的抑制效果。对PA-pH-TEMPO和DOX@PA-pH-TEMPO的体外细胞摄取实验表明,HeLa细胞对材料具有良好的摄取效果,并可检测到明显的EPR信号。

     

  • 图  1  单体12的合成路线

    Figure  1.  Synthetic routes of derivatives 1 and 2

    图  2  pH响应型载药胶束的示意图(a)和PA-pH-TEMPO与TEMPOL的EPR谱图(b)

    Figure  2.  Schematic illustration of the pH-sensitive DOX-loading micelles (a) and EPR of PA-pH-TEMPO and TEMPOL (b)

    图  3  单体12和聚合物PA-pH-TEMPO的1H-NMR谱(a)和FT-IR谱(b)

    Figure  3.  1H-NMR (a) and FT-IR (b) spectra of 1, 2 and PA-pH-TEMPO

    图  4  PA-pH-TEMPO(a)和DOX@PA-pH-TEMPO(b)的TEM图像

    Figure  4.  TEM images of PA-pH-TEMPO (a) and DOX@PA-pH-TEMPO (b)

    图  5  37 ℃下载药胶束DOX@PA-pH-TEMPO在不同pH的PBS介质中的体外累积释放曲线

    Figure  5.  In vitro drug release profiles of DOX@PA-pH-TEMPO at 37 ℃ in PBS buffer at different pH

    图  6  载药胶束和阿霉素对HeLa细胞培养24 h(a) ,48 h(b) ,72 h(c) 和对L929细胞培养72 h(d)时的体外细胞活性

    Figure  6.  In vitro cytotoxicity of DOX and DOX@PA-pH-TEMPO against HeLa after 24 h(a), 48 h(b), 72 h incubation (c) and against L929 after 72 h incubation (d)

    图  7  DOX@PA-pH-TEMPO培养4 h后HeLa细胞的CLSM图像(a);TEMPOL和PA-pH-TEMPO培养后的细胞液的EPR谱图(b)

    Figure  7.  CLSM images of HeLa cells after incubation with DOX@PA-pH-TEMPO for 4 h(a) ; EPR spectra of cell suspension after incubating with TEMPOL and PA-pH-TEMPO, respectively(b)

    表  1  空白胶束及载药胶束的性能

    Table  1.   Properties of the blank and DOX-loaded micelles

    Type LC/% EE/% Size/nm PDI Zeta potential/mV
    Blank micelle 227.1 0.220 9.16
    DOX-loaded micelle 2.58 32.09 298.0 0.146 7.93
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出版历程
  • 收稿日期:  2018-07-30
  • 网络出版日期:  2019-10-09
  • 刊出日期:  2019-12-01

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