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化学进展 2022, Vol. 34 Issue (4): 837-845 DOI: 10.7536/PC210446 前一篇   后一篇

• 综述 •

小分子共价DNA的组装及生物医学应用

马佳慧1, 袁伟1, 刘思敏1, 赵智勇1,2,*()   

  1. 1 武汉科技大学 化学与化工学院 耐火材料与冶金国家重点实验室 武汉 430081
    2 湖北师范大学 污染物分析与资源化技术湖北省重点实验室 黄石 435002
  • 收稿日期:2021-04-25 修回日期:2021-06-25 出版日期:2022-04-24 发布日期:2021-07-29
  • 通讯作者: 赵智勇
  • 基金资助:
    国家自然科学基金项目(21604066); 国家自然科学基金项目(21871216); 湖北省教育厅科学技术研究项目(B2016012)
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Self-Assembly of Small Molecule Modified DNA and Their Application in Biomedicine

Jiahui Ma1, Wei Yuan1, Simin Liu1, Zhiyong Zhao1,2()   

  1. 1 The State Key Laboratory of Refractories and Metallurgy, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology,Wuhan 430081, China
    2 Hubei Key Laboratory of Pollutant Analysis & Reuse Technology, Hubei Normal University,Huangshi 435002, China
  • Received:2021-04-25 Revised:2021-06-25 Online:2022-04-24 Published:2021-07-29
  • Contact: Zhiyong Zhao
  • Supported by:
    National Natural Science Foundation of China(21604066); National Natural Science Foundation of China(21871216); Research Project of Hubei Provincial Department of Education(B2016012)

DNA,由于其精确的碱基互补配对、良好的生物相容性、稳定的物理化学性质,不仅可用于组装各种形状和尺寸的纳米结构,而且可以设计动态的纳米器件。为了进一步拓展DNA的应用,可通过化学修饰引入功能分子或基团,从而实现二者功能的集成。目前,DNA与高分子、树状分子、多肽和蛋白等共价有机杂化体的合成、组装及在药物运输和控释等领域的应用已研究得比较成熟,而结构和功能多样的小分子与DNA共价杂化体,由于疏水小分子体积小,其组装受到限制,近年来科研者通过结构衍生或增多芳香环等研究其组装行为及应用。本文主要综述了疏水小分子共价连接DNA后的组装行为及其在生物医药领域的潜在应用,并对这类杂化体纳米材料的研究前景进行了展望。

关键词： DNA-小分子杂化体, 共价连接, 组装调控, 生物医学应用

Due to the addressability, programmability and excellent biocompatibility, DNA has been applied not merely in constructing static elegant nanostructures with different shapes and sizes, but also in designing dynamic nanodevices. Moreover, to further expand the application of DNA, functional groups or molecules can be conjugated with DNA through chemical modification. DNA could combine with hydrophobic organic molecules to be a new amphiphilic building block and then self-assemble into nanomaterials. So far, DNA has been covalent with polymers, dendrimers, peptides or proteins, and the assembly behavior and potential application of these hybrids have been widely investigated. Of particular note, recent state-of-the-art research has turned our attention to the amphiphilic DNA organic hybrids, including small molecule modified DNA (lipid-DNA, fluorescent molecule-DNA, etc.). This review focuses mainly on the development of their self-assembly behavior and their potential application in biomedicine. The potential challenges regarding the amphiphilic DNA organic hybrids are also briefly discussed, aiming to advance their practical applications in nanoscience and biomedicine.

Contents

1 Introduction

2 Self-assembly of small molecule modified DNA

2.1 Self-assembly of amphiphilic DNA-small molecule hybrid

2.2 Self-assembly of supramolecular DNA amphiphiles through host-guest interaction

3 Application of small molecule modified DNA assemblies in biomedicine

3.1 Drug release

3.2 Target delivery

3.3 Biosensor

4 Conclusion and outlook

Key words: small molecule modified DNA, conjugate, assembly and control, biomedicine application
()
图1 (a)DNA-脂质体组装形成囊泡,通过DNA链杂交(DNA2)和链入侵方式(DNA3)实现形貌可逆调控[32]。(b)稳定性可调DNA胶束示意图。分子间G-四链体稳定DNA胶束,不易被血清蛋白破坏;在紫外光照射下,形成G-C配对的双链结构,导致血清蛋白中胶束解离[34]
Fig. 1 (a) DNA-programmed lipid assembles to form spherical lamellar vesicles capable of switching phase to form small spherical micelles in a fully reversible fashion via DNA hybridization (+ DNA2 ) and strand invasion (+ DNA3 ) cycles[32]. (b)Schematic of stability-tunable DNA micelles. Intermolecular G-quadruplex stabilizes DNA micelles against disruption by serum albumin. Upon exposure to UV light, C6-cDNA is released to block the formation of G-quadruplex, resulting in the dissociation of micelles in serum albumin[34]
图2 (a)D18-PDI共轭体系的自组装和基于主客体作用的可逆形态变化[38]。(b)DNA接枝的超分子聚合物和芘单元的化学结构[40]
Fig. 2 (a) The self-assembly process of D18-PDI conjugates and the reversible morphological change based on the host-guest interaction[38]. Reproduced from Ref. [38] with permission from The Royal Society of Chemistry. (b) A DNA-grafted supramolecular polymer and the chemical structure of pyrene units[40]
图3 (a)固相“点击”化学方法合成DNA1~3两亲化合物,并且他们可逆的自组装成具有增强发射的表面工程囊泡[43]。(b)基于DNA的两亲性分子自组装成具有M螺旋性的DNA修饰的扭曲纳米带示意图[47]
Fig. 3 (a) Solid-phase “click” chemistry approach for the synthesis of DNA1~3 amphiphiles and their reversible self-assembly into surface-engineered vesicles with enhanced emission[43]. (b) Schematic for the self-assembly of DNA-based amphiphiles into DNA-decorated, twisted nanoribbons with M-helicity[47]
图4 (a)基于环糊精主客体化学构筑的超两亲DNA结构及其组装[52]。(b)基于葫芦[7]脲的主客体化学构筑具有刺激响应性的超两亲DNA结构及其自组装[54]
Fig. 4 (a) Schematic representation illustrating the “click” chemistry based synthesis of DNA1 or -2-β-CD and non-covalent synthesis of DNA1 or -2-β-CD/1 or 2. Amphiphilicity-driven self-assembly of DNA1 or -2-β-CD/1 or 2 into DNA-decorated vesicles is also shown[52]. Reproduced from Ref. [52] with permission from The Royal Society of Chemistry.(b)The modular construction and self-assembly of DNA supra-amphiphiles through host-guest interaction and their stimuli responsiveness[54]
图5 (a)可转换适配体胶束耀斑的工作原理。没有靶分子情况下,适配体探针保持茎环结构,荧光猝灭;与靶结合后,可转换适配体的构象,荧光信号恢复[57]。(b)光不稳定的两亲DNA药物纳米结构示意图[59]。(c)DNA-PE的化学结构和两亲性驱动的DNA-PE自组装成囊泡及其细胞摄取图[61]
Fig. 5 (a) Working principle of switchable aptamer micelle flares. In the absence of target, the aptamer switch probe maintains a loop-stemstructure, and fluorescence is quenched. Upontarget binding, the conformation of switchable aptamer is altered, resulting in the restoration of fluorescence signal[57]. (b) Schematics of the DNA-drug nanostructures assembled from photolabile DNA-drug amphiphiles[59]. (c) Chemical structure of DNA-PE and a schematic representation depicting the amphiphilicity-driven self-assembly of DNA-PE into vesicular nanostructures, and their cellular uptake[61]
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