基于TACMAA化学的肿瘤微酸性环境响应高分子纳米药物载体

李洪军; 刘晶; 杜金志; 王均

doi:10.11777/j.issn1000-3304.2019.18268

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基于TACMAA化学的肿瘤微酸性环境响应高分子纳米药物载体

综述 | 更新时间：2021-01-26

- 基于TACMAA化学的肿瘤微酸性环境响应高分子纳米药物载体
- TACMAA Chemistry-based Tumor Extracellular pH-responsive Polymeric Nanomaterials for Drug Delivery
- 高分子学报 2019年50卷第6期页码：567-574
- 作者机构：
  
  1.华南理工大学生物医学科学与工程学院生命科学研究院　广州 510006
  2.中国科学技术大学生命科学学院　合肥 230026
- 作者简介：
  
  E-mail: djzhi@scut.edu.cn
  E-mail: mcjwang@scut.edu.cn
- 基金信息：
  
  国家重点研发计划(项目号2017YFA0205600)、国家自然科学基金(基金号 51633008, 31771091)和广东省杰出青年基金(基金号 2017A030306018)资助项目()
- DOI：10.11777/j.issn1000-3304.2019.18268
  中图分类号：
- 纸质出版日期：2019-6，
  
  网络出版日期：2019-4-28，
  
  收稿日期：2018-12-14，
  
  修回日期：2019-3-16，
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李洪军, 刘晶, 杜金志, 王均. 基于TACMAA化学的肿瘤微酸性环境响应高分子纳米药物载体[J]. 高分子学报, 2019,50(6):567-574.

Hong-jun Li, Jing Liu, Jin-zhi Du, Jun Wang. TACMAA Chemistry-based Tumor Extracellular pH-responsive Polymeric Nanomaterials for Drug Delivery[J]. Acta Polymerica Sinica, 2019,50(6):567-574.
李洪军, 刘晶, 杜金志, 王均. 基于TACMAA化学的肿瘤微酸性环境响应高分子纳米药物载体[J]. 高分子学报, 2019,50(6):567-574. DOI： 10.11777/j.issn1000-3304.2019.18268.

Hong-jun Li, Jing Liu, Jin-zhi Du, Jun Wang. TACMAA Chemistry-based Tumor Extracellular pH-responsive Polymeric Nanomaterials for Drug Delivery[J]. Acta Polymerica Sinica, 2019,50(6):567-574. DOI： 10.11777/j.issn1000-3304.2019.18268.

摘要

过去几十年，纳米技术在药物递送、分子影像、肿瘤治疗等领域获得了广泛的应用. 相比小分子药物，纳米药物具有提高药物成药性、改善药物分布、降低毒副作用等特点，但是，纳米药物需面临复杂的体内递送过程，才能最终到达靶部位发挥药效. 有针对性地设计高分子载体材料的结构，使其对体内微环境产生特异性的响应以改变纳米载体性能，适应体内药物递送复杂环境，是提高纳米药物递送效率的重要策略. 本文系统介绍了我们如何思考归纳纳米药物体内递送的复杂过程，并进一步提出基于肿瘤组织酸性微环境调控纳米载体性能以提高药物递送效率这一核心思想. 详细回顾了基本设想的提出、验证到体内效果的系统性评估，以及基于这一思想发展的多种药物递送策略，从多个层面解决体内药物输送面临的难题，并对此领域未来的发展进行了展望.

Abstract

Over the past decades

nanotechnology has been intensively investigated for application in drug delivery

cancer treatment

and cancer diagnostics. Treatment with cancer nanomedicines have shown many benefits in improving clinical translation potential and drug biodistribution

reducing side effects and improving the life quality of patients

compared with that by small-molecule anticancer therapeutics. However

a series of complex biological barriers

including the blood barriers

tumor microenvironment barriers

intratumor cell barriers considerably prevent a nanomedicine from reaching its targets in a sufficient concentration and thus severely limit its therapeutic benefits. A feasible strategy is to formulate the nanocarriers in response to microenvironment and to tune their properties to adapt to each individual environment for robust and effective delivery. In this review

we systemically summarize the principles of nanoparticle design for overcoming multiple biological barriers in drug delivery

and conclude the ideal properties of nanomedicine and its biological effects in the microenvironment of each stage

such as blood

extracellular region and intratumor cell in drug delivery. This can guide the development of intelligent nanomedicine which can overcome the drug delivery barriers by making subtle response to the changes of physiological signal. In this review

we highlight some typical strategies we developed in recent 10 years

especially the nanocarriers response to the acidic extracellular environment

to improve the delivery efficiency after systemic administration

including surface charge reversal

surface PEG detachment

particle size transition and ligand reactivation. Finally

the opportunities and challenges in tumor responsive nanomedicines are also disscussed.

关键词

纳米药物pH响应性药物载体与递送肿瘤微环境

Keywords

NanomedicinepH-responsiveDrug deliveryTumor microenvironment

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