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化学进展 2021, Vol. 33 Issue (10): 1887-1899 DOI: 10.7536/PC200921 前一篇   后一篇

• 综述 •

DNA水凝胶在生物传感中的应用和发展

张开宇1, 高国伟1,2, 李延生1,3,*(), 宋钰1, 温永强4,*(), 张学记5   

  1. 1 北京信息科技大学传感器重点实验室 北京 100101
    2 北京信息科技大学 现代测控技术教育部重点实验室 北京 100192
    3 中国科学院仿生材料与界面科学重点实验室(理化技术研究所) 北京 100190
    4 北京科技大学化学与生物工程学院 北京 100083
    5 深圳大学生物医学工程学院 深圳 518060
  • 收稿日期:2020-09-10 修回日期:2020-11-05 出版日期:2021-10-20 发布日期:2020-12-22
  • 通讯作者: 李延生, 温永强
  • 基金资助:
    中国科学院仿生材料与界面科学重点实验室开放课题和国家自然科学基金项目(61901042); 中国科学院仿生材料与界面科学重点实验室开放课题和国家自然科学基金项目(21975019); 中国科学院仿生材料与界面科学重点实验室开放课题和国家自然科学基金项目(31870816)
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Development and Application of DNA Hydrogel in Biosensing

Kaiyu Zhang1, Guowei Gao1,2, Yansheng Li1,3(), Yu Song1, Yongqiang Wen4(), Xueji Zhang5   

  1. 1 Key Laboratory of Sensors, Beijing Information Science and Technology University,Beijing 100101,China
    2 MOE Key Laboratory of Modern Measurement and Control Technology, Beijing Information Science and Technology University,Beijing 100192, China
    3 CAS Key Laboratory of Bio-inspired Materials and Interfacial Science, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences,Beijing 100190, China
    4 School of Chemistry and Biological Engineering,University of Science and Technology Beijing,Beijing 100083, China
    5 School of Biomedical Engineering, Shengzhen University,Shenzhen 518060, China
  • Received:2020-09-10 Revised:2020-11-05 Online:2021-10-20 Published:2020-12-22
  • Contact: Yansheng Li, Yongqiang Wen
  • Supported by:
    CAS Key Laboratory of Bio-inspired Materials and Interfacial Science, Chinese Academy of Sciences and National Natural Science Foundation of China(61901042); CAS Key Laboratory of Bio-inspired Materials and Interfacial Science, Chinese Academy of Sciences and National Natural Science Foundation of China(21975019); CAS Key Laboratory of Bio-inspired Materials and Interfacial Science, Chinese Academy of Sciences and National Natural Science Foundation of China(31870816)

脱氧核糖核酸(DNA)是一种重要的生物分子,具有许多独特的性质如:信息传递、分子识别、可编辑等。DNA水凝胶同时具有DNA分子和水凝胶材料的优势,并且可以引入其他纳米材料获得多功能杂化水凝胶。相比于传统水凝胶,DNA水凝胶具有良好的特异识别能力以及可以按需设计的性质,从而被广泛应用于生物传感领域。本文围绕DNA水凝胶的合成、响应机制以及在传感领域的应用进行综述。按照不同的合成方法可分为线性DNA链缠绕水凝胶、枝状DNA自组装水凝胶、杂合DNA水凝胶。根据传感机制的不同又可以分为包埋封装法和非包埋封装法,包埋封装发法又分为:酶的包埋释放、抗原-抗体的包埋释放、纳米材料的包埋释放。本文总结了近几年DNA水凝胶在重金属离子检测、核酸检测、葡萄糖检测、蛋白质和代谢小分子检测,以及细胞检测等热门领域的研究情况,最后对其未来的发展进行了展望。

关键词： DNA水凝胶, 生物传感, 智能水凝胶, 特异性识别

Deoxyribonucleic acid(DNA) is an important biological molecule with many unique properties such as information transmission, molecular recognition, editability, etc. DNA hydrogels have the advantages of both DNA molecules and the hydrogel materials, and can introduce other nanomaterials to obtain multifunctional hybrid hydrogels. Compared with traditional hydrogels, DNA hydrogels have good specific recognition ability and the properties that can be designed on demand, so they are widely used in the field of biosensing. This article reviews the synthesis, response mechanism and application of DNA hydrogels in the field of sensing. According to different synthesis methods, DNA hydrogels can be divided into linear DNA strand interwinded hydrogel, dendritic DNA self-assembly hydrogel, and hybrid DNA hydrogel. According to the different sensing mechanism, DNA hydrogels can be divided into encapsulation type DNA hydrogels and non-encapsulation type DNA hydrogels. The encapsulation method is divided into: enzyme embedding release, antigen-antibody embedding release, and nanomaterial embedding release. This article summarizes the application and research of DNA hydrogels in the detection of heavy metal ions, nucleic acid detection, glucose detection, protein and metabolic small molecule detection, and cell detection in recent years, and finally prospects its future development.

Contents

1 Introduction

2 Synthesis of DNA Hydrogel

2.1 Ultralong linear DNA intertwined hydrogel

2.2 Dendritic DNA assembled hydrogel

2.3 Hybrid DNA hydrogel

3 Biosensing mechanisms

3.1 Encapsulation

3.2 Non-encapsulation

4 Application of DNA hydrogel biosensing device

4.1 Environmental monitoring

4.2 DNA hydrogel for medical sensing

5 Conclusion and outlook

Key words: DNA hydrogel, biosensing, intelligent hydrogels, specific recognition
()
图1 DNA引发剂触发自组装过程[41]。(A)发夹链H1二聚体和H2以及引发剂链Ⅰ的结构。(B)钳制杂交链反应。(C)水凝胶的形成过程
Fig. 1 Design principle of the DNA initiator triggered self-assembly process[41].(A) Structures of the hairpin strands H1-dimer and H2, and strand Ⅰ.(B) Details of the C-HCR process initiated by Ⅰ.(C) Hydrogel formation process
图2 DNA水凝胶工作过程[55]。当存在腺苷时,腺苷与Acry-A-Apt的结合导致DNA水凝胶的完全裂解,释放出G-四链体/血红素和Au @HKUST-1
Fig. 2 DNA hydrogel working process[55]. When adenosine is present, the binding of adenosine to Acry-A-Apt results in complete cleavage of the DNA hydrogel, releasing G-quadruplex/heme and Au @HKUST-1
图3 (A)DNA水凝胶检测Pb2+示意图。(B)DNA水凝胶薄膜制备[65]
Fig. 3 (A) Schematic illustration of the DNA-based hydrogel for the detection of Pb2+.(B) DNA hydrogel film is formed[65]
图4 DNA水凝胶的特异性。(A)水凝胶对1 mM阳离子和1μM Pb2+的响应结果。(B)上清液在520 nm处对应的吸光度。(C)DNA水凝胶对海水中不同浓度Pb2+的反应[80]
Fig. 4 Specificity of DNA hydrogel.(A) Response of hydrogel to 1 mM cations and 1 μM Pb2+.(B) The corresponding absorbance at 520 nm of the supernatant.(C) Responses of DNA hydrogel to different concentrations of lead ion in seawater[80]
图5 (A)目标响应DNA水凝胶的体积条形图芯片工作原理;(B)在缓冲液和消化血液中,Pb2+浓度不同,墨条移动的距离不同;(C)墨条距离对Pb2+浓度的线性响应[80]
Fig. 5 (A) The working principle of the target response DNA hydrogel volume bar graph chip;(B) Different travel distance of the ink bar with different concentration of Pb2+ in buffer and digested blood sample;(C) The linear response of ink bar distance to Pb2+ concentration[80]
图6 微囊藻毒素-LR(MC-LR)的检测过程。(A)MC-LR 响应水凝胶的合成过程。(B)特异性适体与 MC-LR 竞争性结合并由于适体与靶标之间的高亲和力形成靶标-适体复合物,导致水凝胶崩解并释放预载的 Cu/Au/Pt TNs[84]
Fig.6 Detection process of microcystin-LR.(A) MC-LR responds to the synthesis process of hydrogel.(B)The specific aptamers competitively binded with the MC-LR and form target-aptamer complexes due to high affinity between aptamer and target, causing the disintegration of hydrogels and the release of preloaded Cu/Au/Pt TNs[84]
图7 (A)自驱动DNA水凝胶传感器的设计/工作原理;(B)自驱动DNA水凝胶传感器的制备过程;(C)传感器对miRNA进行视觉和定量检测的原理[87]
Fig. 7 (A) The designing/working principle of the self-driven DNA hydrogel sensor;(B) The preparation process of the self-driven DNA hydrogel sensor;(C) The principle of the visual and quantitative detection of miRNA by using the proposed sensor[87]
图8 DNA水凝胶快速检测T-2毒素过程[89]。添加T-2毒素改变了适体的结构,导致水凝胶的塌陷生成大量的I2。I2沿纵向刻蚀AuNRs,得到具有不同长径比和颜色的AuNRs
Fig. 8 Schematic depicting the rapid detection of the T-2 toxin with DNA hydrogel[89]. The addition of T-2 toxin changed the structure of aptamers, resulting in the collapse of hydrogels and the formation of large amounts of I2. The AuNRs with different aspect ratio and color were obtained by etching AuNRs along the longitudinal direction with I2
图9 含有AuNPs的式DNA水凝胶的工作原理。在葡萄糖复合物存在时,DNA水凝胶结构被破坏将AuNPs释放到上清液中肉眼便可以看到上清液变为红色[95]
Fig. 9 Working principle of DNA hydrogel containing embedded AuNPs for visual detection of glucose. In the presence of glucose complex, the DNA hydrogel is disrupted and encapsulated AuNPs are released to the supernatant. The supernatant's red color can be observed by the naked eye[95]
图10 适体-配体DNA水凝胶通过启动子诱导杂交链反应[97]。(A)ATP响应水凝胶微胶囊制备;(B)可卡因响应性水凝胶制备;(C)配体驱动解锁适体-桥连水凝胶示意图
Fig. 10 Schematic of aptamer-ligand responsive nucleic acid/acrylamide hydrogels via the promoter-induced hybridization chain reaction(HCR), which crosslinks hairpin-modified acrylamide chains[97].(A) Preparation of ATP-responsive hydrogel microcapsules;(B) Preparation of cocaine-responsive hydrogel microcapsules;(C) Schematic of the ligand-driven unlocking of the aptamer-bridged hydrogel microcapsules
图11 (A)分支DNA构建在表面DNA水凝胶在被诱饵分子修饰后能特异性粘附靶细胞。(B)在玻璃表面形成DNA网络[100]
Fig. 11 (A) DNA hydrogels that are based on branched DNA and built on surfaces adhere specifically cells when they are decorated with bait molecules.(B) The formation of DNA networks on glass surfaces[100]
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