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化学进展 2020, Vol. 32 Issue (7): 927-934 DOI: 10.7536/PC191201 前一篇   后一篇

• 综述 •

基于肿瘤微环境响应的DNA纳米结构递药系统

吴晴1, 唐一源1, 余淼1, 张悦莹2, 李杏梅3,**()   

  1. 1. 中南大学湘雅药学院 长沙 410013
    2. 中南大学生命科学学院 长沙 410013
    3. 中南大学基础医学院法医学教研室 长沙 410013
  • 收稿日期:2019-12-05 出版日期:2020-07-24 发布日期:2020-07-10
  • 通讯作者: 李杏梅
  • 基金资助:
    国家级大学生创新训练项目(201910533105)
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Stimuli-Responsive DNA Nanostructure Drug Delivery System Based on Tumor Microenvironment

Qing Wu1, Yiyuan Tang1, Miao Yu1, Yueying Zhang2, Xingmei Li3,**()   

  1. 1. Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China
    2. School of Life Sciences, Central South University, Changsha 410013, China
    3. Department of Forensic Science, School of Basic Medical Sciences, Central South University, Changsha 410013, China
  • Received:2019-12-05 Online:2020-07-24 Published:2020-07-10
  • Contact: Xingmei Li
  • About author:
    ** e-mail:
  • Supported by:
    National Training Program Innovation for Undergraduates(201910533105)

DNA分子由于其独特的生物相容性和可编程性,在增强药物靶向性和降低药物毒性方面展现了独特的优势和巨大的潜力。随着人们对肿瘤微环境研究的深入和环境响应性的DNA触发器的研制,近些年已报道了许多基于肿瘤微环境响应的DNA纳米结构递药系统,这些DNA纳米结构递药系统结合了纳米运载工具良好的生物分布和药代动力学特性,以及小型药物载体的快速扩散和渗透特性。通过靶向广泛的肿瘤栖息地而不是肿瘤特异性受体,该策略有可能克服肿瘤异质性问题,并可用于设计诊断和治疗多种实体肿瘤的纳米颗粒。在体内能够稳定地转运,在肿瘤组织独特的微环境刺激下释放药物,能有效地控制药物释放部位和释放速度,极大地降低了肿瘤治疗的毒副作用。本文主要从pH响应型、GSH响应型、ATP响应型、酶响应型、抗原响应型五个方面,综述了基于肿瘤微环境响应的DNA纳米结构递药系统的最新研究进展,分类介绍了这些DNA纳米载体的设计策略和响应释放机制,此外,还重点介绍了该领域面临的前景和挑战。

关键词： DNA纳米结构, 肿瘤微环境, 刺激响应, 药物递送

DNA molecules have shown unique advantages and high potential in enhancing drug targeting and reducing drug toxicity because of their unique biocompatibility and programmability. And spurred by the development of tumor microenvironment research and the development of environmentally responsive DNA triggers, many DNA nanostructure delivery systems based on tumor microenvironment have been reported in recent years. These DNA nanostructures combine the favorable biodistribution and pharmacokinetic properties of nanodelivery vehicles and the rapid diffusion and penetration properties of smaller drug cargos. By targeting a wide range of tumor habitats rather than tumor specific receptors, the strategy is likely to overcome the problem of tumor heterogeneity and can be used to design nanoparticles for diagnosis and treatment of multiple solid tumors. They can be transported steadily in the blood circulation, releasing drugs under the unique microenvironmental stimulation of tumor tissue, effectively controlling the drug release site and release speed, and greatly reducing the toxic and side effects of tumor treatment. In this article, the latest research progress of tumor microenvironment responsive DNA nanostructure drug delivery systems is reviewed from five aspects of pH responsive systems, GSH responsive systems, ATP responsive systems, enzyme responsive systems, and antigen responsive systems. The design strategy and responsive release mechanism of corresponding DNA nanocarriers are discussed in great detail. In addition, the prospects and main challenges in this area are also discussed.

Contents

1 Introduction

2 Stimuli-responsive DNA Nanostructure drug delivery system

2.1 GSH responsive systems

2.2 ATP responsive systems

2.3 Enzyme responsive systems

2.4 pH responsive systems

2.5 Antigen responsive systems

3 Conclusion and outlook

Key words: DNA nanostructure, tumor microenvironment, stimuli-responsive, drug delivery
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图1 还原环境响应的紫杉醇胶束[14]
Fig.1 GSH responsive spherical nucleic acids[14]
图2 GSH响应的双束DNA四面体释放反义寡核苷酸[19]
Fig.2 GSH responsive double-bundle DNA tetrahedron for antisense oligonucleotides delivery[19]
图3 ATP响应的负载核酸的二硫化钼薄片[27]
Fig.3 ATP responsive nucleic acid loaded 2D MoS2 Nanosheets[27]
图4 端粒酶响应的核壳结构生物聚合物[33]
Fig.4 Telomerase responsive nuclear-shell biopolymers[33]
图5 pH响应的DNA折纸胶囊[38]
Fig.5 pH responsive DNA origami capsule[38]
图6 pH响应的纳米负载纳米颗粒[44]
Fig.6 pH responsive nanoparticle-loaded nanoparticles[44]
图7 间接的pH响应性DNA纳米海绵[46]
Fig.7 Indirect pH reponsive DNA nano-sponge[46]
图8 凝血酶功能化DNA纳米机器人的设计与表征[53]
Fig.8 Design and characterization of thrombin-functionalized DNA nanorobot[53]
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