高分子抗肿瘤纳米药物的挑战与发展

孙瑞; 邱娜莎; 申有青

doi:10.11777/j.issn1000-3304.2019.19005

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高分子抗肿瘤纳米药物的挑战与发展

综述 | 更新时间：2021-01-26

- 高分子抗肿瘤纳米药物的挑战与发展
- Polymeric Cancer Nanomedicines: Challenge and Development
- 高分子学报 2019年50卷第6期页码：588-601
- 作者机构：
  
  浙江大学化学工程与生物工程学院生物纳米工程中心　杭州 310027
- 作者简介：
  
  E-mail: shenyq@zju.edu.cn You-qing Shen, E-mail: shenyq@zju.edu.cn
- 基金信息：
  
  国家自然科学基金(基金号 U1501243，21704090，51833008)资助项目()
- DOI：10.11777/j.issn1000-3304.2019.19005
  中图分类号：
- 纸质出版日期：2019-6，
  
  网络出版日期：2019-4-3，
  
  收稿日期：2019-1-8，
  
  修回日期：2019-2-11，
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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.

Rui Sun, Na-sha Qiu, You-qing Shen. Polymeric Cancer Nanomedicines: Challenge and Development[J]. Acta Polymerica Sinica, 2019,50(6):588-601.
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.

Rui Sun, Na-sha Qiu, 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.

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

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

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.

Abstract

At present

cancer nanomedicine mainly focuses on mitigating adverse effects but fails to enhance the therapeutic efficacies of anticancer drugs. With the benchmark of the recent highly effective molecular targeted therapies and immunotherapies

rational design of next-generation cancer nanomedicine should aim at enhancing its therapeutic efficacy. From this point of view

this review first analyszs the typical cancer-drug-delivery process of an intravenously administered nanomedicine and concludes as a cascade of five steps

including circulation in the blood compartments

accumulation in the tumor

subsequent penetration deep into the tumor tissue to reach tumor cells

internalization into those cells

and finally intracellular drug release (CAPIR cascade for short). High efficiency of every step is critical for a nanomedicine to achieve a high overall delivery efficiency and thereby improve the whole therapeutic efficiency. Further analysis shows that to maximize its efficiency

the nanoproperties required in each step for a nanomedicine are different and even opposite in different steps

such as PEG

surface-charge

size

and stability dilemmas. To resolve these dilemmas and integrate all the required nanoproperties into one nanomedicine

stability

surface

and size nanoproperty transitions (

transitions for short) are proposed. Stimulus-responsive polymers have been designed to realize the

transitions

including pH-

ROS-

redox-

enzyme-responsive

and so on. Smart nanomedicines possessing the

transitions are demonstrated. The challenges in designing high-performance cancer nanomedicines and their clinical translations are then discussed. Clinical translation is the ultimate goal of nanomedicine research. To design translational nanomedicines

the three key elements

transition capability

material excipientability

and process scale-up ability (CES elements for short) must be considered. Our recent development of noncytotoxic with highly potent therapeutic polymers as a new type of molecular nanomedicine is summarized. Finally

by comparing viral vectors

a possible solution for multifunctional nanomedicines to realize their clinical translation is proposed.

关键词

纳米药物功能高分子肿瘤靶向输送纳米特性转换治疗性高分子分子纳米药物

Keywords

NanomedicineFunctional polymersTumor-targeting delivery3S nanoproperty transitionsCopper sequestrationMolecular nanomedicine

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