ISSN 1000-3304CN 11-1857/O6

高分子抗肿瘤纳米药物的挑战与发展

孙瑞 邱娜莎 申有青

引用本文: 孙瑞, 邱娜莎, 申有青. 高分子抗肿瘤纳米药物的挑战与发展[J]. 高分子学报, 2019, 50(6): 588-601. doi: 10.11777/j.issn1000-3304.2019.19005 shu
Citation:  Rui Sun, Na-sha Qiu and You-qing Shen. Polymeric Cancer Nanomedicines: Challenge and Development[J]. Acta Polymerica Sinica, 2019, 50(6): 588-601. doi: 10.11777/j.issn1000-3304.2019.19005 shu

高分子抗肿瘤纳米药物的挑战与发展

    通讯作者: 申有青, E-mail: shenyq@zju.edu.cn
  • 基金项目: 国家自然科学基金(基金号 U1501243,21704090,51833008)资助项目

摘要: 抗肿瘤纳米药物的理想目标是降低毒副作用并提高疗效,但目前临床用纳米药物主要以显著降低药物毒性的优势获批进入临床. 近年来,肿瘤分子靶向治疗、免疫治疗等高疗效方法的飞速发展,使提高疗效成为抗肿瘤纳米药物研究的当务之急. 静脉注射的纳米药物向实体肿瘤靶向输送过程是血液系统内循环、从血管外渗进入肿瘤组织和蓄积、肿瘤组织内渗透、肿瘤细胞内吞、胞内药物释放的五步“级联”递送过程(即CAPIR cascade). 因此,如何设计载体高分子的功能,赋予纳米药物随血液系统、肿瘤组织和肿瘤细胞的微环境的变化而改变其纳米尺寸(size)、表面(surface)和稳定性(stability) (即3S nanoproperty transitions),从而满足肿瘤靶向输送过程中各步的要求以确保每一步具有高的效率,是获得高肿瘤靶向输送效率和高疗效的关键. 本文将介绍利用各种响应高分子包括作者提出的电荷反转型高分子来设计具有上述3S纳米特性转换能力的高效纳米药物的方法,并总结了今后高分子纳米药物研究面临的挑战和发展趋势.

English

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  • Figure 1.  Summary of the CAPIR cascade and the 3S nanoproperty transitions for a nanomedicine to have high overall drug-delivery efficiency (Reprinted with permission from Ref.[5]; Copyright (2017) John Wiley and Sons)

    Figure 2.  pH-Responsive units

    Figure 3.  The structures of amidized polylysine (PLL) with 1,2-dicarboxylic-cyclohexene anhydride (PLL/DCA), 2,3-dimethylmaleic anhydride (PLL/DM), and 2,2,3,3-tetramethylsuccinic anhydride (PLL/TM) and their hydrolysis and charge-reversal kinetics at different acidities (Reprinted with permission from Ref.[16]; Copyright (2009) John Wiley and Sons)

    Figure 4.  Redox-responsive units

    Figure 5.  ROS-cleavable polysulfonium (Reprinted with permission from Ref.[43]; Copyright (2017) John Wiley and Sons)

    Figure 6.  Schematic representation of ROS-responsive charge-reversal polymer and its targeting fusogenic lipopolyplex (RGDK-FLPPs) for systemic gene delivery (Reprinted with permission from Ref.[28]; Copyright (2015) John Wiley and Sons)

    Figure 7.  Enzyme-responsive nanomaterials for 3S nanopropety transitions (Reprinted with permission from Ref.[63]; Copyright (2014) The Royal Society of Chemistry)

    Figure 8.  Illustration of esterase responsive charge-reversal polymer and its lipid-coated esterase responsive polyplexes with TRAIL plasmid for cancer gene therapy (Reprinted with permission from Ref.[70]; Copyright (2016) John Wiley and Sons)

    Figure 9.  Three key CES elements: capability (C), material excipientability (E), and process scale-up ability (S) for designing translational nanomedicine

    Figure 10.  (a) Copper activates tumor proliferation, metastasis, and angiogenesis related signals; (b) The targeted copper-depletion based anticancer therapy

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  • 通讯作者:  申有青, shenyq@zju.edu.cn
  • 收稿日期:  2019-01-08
  • 修稿日期:  2019-02-11
  • 网络出版日期:  2019-04-03
  • 刊出日期:  2019-06-01
通讯作者: 陈斌, bchen63@163.com
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