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  • CN 31-1691/TQ

pH/光双敏感含偶氮苯聚合物分子的设计及药物载体的应用

刘天奇 雷彬 徐首红 刘洪来

刘天奇, 雷彬, 徐首红, 刘洪来. pH/光双敏感含偶氮苯聚合物分子的设计及药物载体的应用[J]. 华东理工大学学报(自然科学版), 2021, 47(2): 137-146. doi: 10.14135/j.cnki.1006-3080.20191227005
引用本文: 刘天奇, 雷彬, 徐首红, 刘洪来. pH/光双敏感含偶氮苯聚合物分子的设计及药物载体的应用[J]. 华东理工大学学报(自然科学版), 2021, 47(2): 137-146. doi: 10.14135/j.cnki.1006-3080.20191227005
LIU Tianqi, LEI Bin, XU Shouhong, LIU Honglai. Design and Drug Carrier Application of a Photo-Responsive and pH-Sensitive Azobenzene Polymer Molecule[J]. Journal of East China University of Science and Technology, 2021, 47(2): 137-146. doi: 10.14135/j.cnki.1006-3080.20191227005
Citation: LIU Tianqi, LEI Bin, XU Shouhong, LIU Honglai. Design and Drug Carrier Application of a Photo-Responsive and pH-Sensitive Azobenzene Polymer Molecule[J]. Journal of East China University of Science and Technology, 2021, 47(2): 137-146. doi: 10.14135/j.cnki.1006-3080.20191227005

pH/光双敏感含偶氮苯聚合物分子的设计及药物载体的应用

doi: 10.14135/j.cnki.1006-3080.20191227005
基金项目: 国家自然科学基金(21776071)和国家自然基金创新研究群体资助项目(51621002)
详细信息
    作者简介:

    刘天奇(1994-),男,硕士生,主要研究方向为智能型纳米药物载体。E-mail:575543407@qq.com

    通讯作者:

    徐首红,E-mail:xushouhong@ecust.edu.cn

  • 中图分类号: O69

Design and Drug Carrier Application of a Photo-Responsive and pH-Sensitive Azobenzene Polymer Molecule

  • 摘要: 采用原子转移自由基聚合(ATRP)法合成了一系列具有pH/光双敏感的两亲性嵌段聚合物C10-偶氮苯(AZO)-C10-聚甲基丙烯酸二异丙胺基乙酯(PDPAn)-聚乙二醇(PEG45)(n=30,50,80),用核磁、凝胶渗透色谱(GPC)对合成的聚合物进行表征,用动态光散射(DLS)测定聚合物自组装形成的胶束的粒径及电位,用紫外分光光度计测定聚合物的光敏感性以及聚合物胶束的pH敏感点,采用荧光分光光度计测定聚合物胶束的临界胶束浓度(CMC),模拟体外阿霉素释药。结果表明,合成的聚合物具有良好的pH敏感性和紫外可见光敏感性,并可以自组装得到粒径约为140~200 nm的均一、稳定的球状胶束,pH敏感点在6.3~7.2之间,并且在波长为365 nm和470 nm的两种光线下发生顺反结构的转变。选择pH敏感点在6.3左右的聚合物胶束运载抗癌药物阿霉素,后续体外释药实验表明聚合物胶束在pH或光刺激下可以很好地实现可控性释药,同时利用细胞毒性实验验证了聚合物胶束具有很低的细胞毒性,该聚合物有望成为一种潜在的pH/光响应型靶向药物载体。

     

  • 图  1  嵌段聚合物合成路线

    Figure  1.  Synthesis route of C10-AZO-C10-PDPAn-mPEG45 block copolymer

    图  2  (Ⅰ) C10-AZO-C10-OBr、(Ⅱ) C10-AZO-C10-PDPAn 和(Ⅲ) C10-AZO-C10-PDPAn-mPEG45在CDCl3中的1H-NMR谱图

    Figure  2.  1H-NMR spectra of (Ⅰ) C10-AZO-C10-OBr, (Ⅱ) C10-AZO-C10-PDPAn and (Ⅲ) C10-AZO-C10-PDPAn-mPEG45 in CDCl3

    图  3  不同pH环境下聚合物胶束溶液的(a)透射率及(b)Zeta电位的变化(聚合物胶束溶液质量浓度0.1 mg/mL)

    Figure  3.  (a) Transmittance and (b) Zeta potential of polymeric micelle solution in different pH environments(Mass concentration of copolymeric micelle solution: 0.1 mg/mL)

    图  4  反式 (a) C10-AZO-C10-PDPA30-mPEG45, (c) C10-AZO-C10-PDPA50-mPEG45, (e) C10–AZO-C10-PDPA80-mPEG45受到不同时间紫外光(365 nm)照射后的紫外吸收谱图; 顺式 (b) C10-AZO-C10-PDPA30-mPEG45, (d) C10-AZO-C10-PDPA50-mPEG45, (f) C10-AZO-C10-PDPA80-mPEG45受不同时间可见光(470 nm)照射后的紫外吸收谱图

    Figure  4.  Ultraviolet absorption spectra after irradiation of ultraviolet (365 nm) after different time intervals of trans-(a) C10-AZO-C10-PDPA30-mPEG45, (c) C10-AZO-C10-PDPA50-mPEG45, (e) C10-AZO-C10-PDPA80-mPEG45; Ultraviolet absorption spectra after irradiation of visible light (470 nm) after different time intervals of cis-(b) C10-AZO-C10-PDPA30-mPEG45, (d) C10-AZO-C10-PDPA50-mPEG45, (f) C10-AZO-C10-PDPA80-mPEG45

    图  5  (a)聚合物C10-AZO-C10-PDPAn-mPEG45n=30,50,80)的临界胶束浓度随荧光强度比值I373/I384变化曲线(pH=7.4);(b)聚合物胶束的粒径分布图(pH=7.4);(c) 聚合物胶束的透射电镜图(pH=7.4)

    Figure  5.  (a) Florescence intensity ratio (I373/I384) versus logarithm of critical micelles concentrations(C10-AZO-C10-PDPAn-mPEG45n=30,50,80)); (b) Size distribution of the copolymer micelles; (c) Transmission electron micrographs of copolymer micelles (pH=7.4)

    图  6  聚合物C10-AZO-C10-PDPA30-mPEG45在不同pH和紫外光照射条件下的累计释放曲线

    Figure  6.  Accumulated release curves of C10-AZO-C10-PDPA30-mPEG45 in different pH under irradiation of UV light

    图  7  不同质量浓度的聚合物空白胶束对Huh7和 HEK-293T的细胞毒性

    Figure  7.  Cytotoxicity to Huh7 and HEK-293T cells at different massconcentrations of copolymer micelle

    表  1  C10-AZO-C10-PDPAn-mPEG45共聚物的分子量和分散系数

    Table  1.   Molecular weight and dispersity index(PDI) of C10-AZO-C10-PDPAn-mPEG45 copolymers

    CopolymerMn,NMRMn,GPCPDI
    C10-AZO-C10-PDPA30-mPEG45889497481.73
    C10-AZO-C10-PDPA50-mPEG4513160113551.82
    C10-AZO-C10-PDPA80-mPEG4519560225241.63
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出版历程
  • 收稿日期:  2019-12-27
  • 网络出版日期:  2020-09-21
  • 刊出日期:  2021-04-02

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