Stimulus-Responsive Multifunctional Nucleic Acid Hydrogels Based on Cell Capture and Release
Received date: 2024-02-22
Revised date: 2024-07-21
Online published: 2024-09-15
Supported by
National Natural Science Foundation of China(22122409)
National Natural Science Foundation of China(22377110)
Henan Province Advantageous Discipline Cultivation Fund Project(222301420019)
Nucleic acid hydrogels have good hydrophilicity, adjustability and biocompatibility, which have attracted considerable attention in the past few years, especially in the field of biomedicine and smart materials. Nucleic acid hydrogel is stimulus-responsive, meaning that external stimuli such as pH changes, light, temperature variations, and chemical triggers (including metal ion response, redox response, and enzyme response) can induce physical and chemical changes within them. Consequently, they are capable of perceiving their environment and undergoing responsive deformation, enabling precise cell therapy that can be controlled both temporally and spatially. Cell capture and release using stimulus-responsive nucleic acid hydrogels can control and modulate cellular behavior, and can also play an important role in biomedical research and applications, such as targeted drug therapies using the capture and release of specific cell types. Based on this, this paper summarizes the preparation methods of pure nucleic acid hydrogels and polymer-nucleic acid hybrid hydrogels, further discusses the application strategies of different stimuli-responsive nucleic acid hydrogels, and focuses on the research progress of cell capture and release in cell imaging, cell therapy and synergistic drug delivery. Finally, we discuss the urgent problems that need to be addressed in the research of nucleic acid hydrogels, and provide a prospect for their future development.
Contents
1 Introduction
2 Preparation of nucleic acid hydrogels
2.1 Pure nucleic acid hydrogel
2.2 Polymer-nucleic acid hybrid hydrogel
3 Stimulus-responsive nucleic acid hydrogels
3.1 pH response
3.2 Light response
3.3 Temperature response
3.4 Chemical trigger
4 Stimulus-responsive nucleic acid hydrogels used for cell capture and release
4.1 Cell imaging
4.2 Cell therapy
4.3 Collaborative drug delivery
5 Conclusion and outlook
Key words: nucleic acid hydrogels; stimulus-responsive; cell capture; cell release; biomedicine
Danyu Wang , Mengke Guo , Zihan Guo , Mengyu Huang , Hua Yi , Kaixiang Zhang . Stimulus-Responsive Multifunctional Nucleic Acid Hydrogels Based on Cell Capture and Release[J]. Progress in Chemistry, 2024 , 36(10) : 1567 -1580 . DOI: 10.7536/PC240216
图1 刺激响应型核酸水凝胶的制备。A)X-DNA、Y-DNA和T-DNA构成的核酸水凝胶[7]。 B)通过RCA合成DNA长单链以获得3D DNA网络的过程[11]。C)通过PNA/DNA络合形成的杂化水凝胶[4]。Fig. 1 Preparation of stimulus-responsive nucleic acid hydrogels. A) Nucleic acid hydrogel composed of X-DNA, Y-DNA, and T-DNA[7]. Copyright 2006, Springer Nature B) The process of synthesizing long single strands of DNA by RCA to obtain a 3D DNA network[11]. Copyright 2020, American Chemical Society C) Heterogeneous hydrogels formed by PNA/DNA complexation[4]. Copyright 2015, Elsevier |
图3 pH、光和温度响应型核酸水凝胶的应用。A)用于制备pH响应型DNA水凝胶的RCA方法的示意图[18]。B)光控DNA交联水凝胶的机理与设计[21]。C)光热响应的MXene-DNA水凝胶的构建示意图及其应用[27]。Fig. 3 Applications of pH, light, and temperature-responsive nucleic acid hydrogels. A) Schematic diagram of the RCA method used to prepare pH-responsive DNA hydrogels[18]. Copyright 2017, John Wiley and Sons B) Mechanism and design of photocontrolled DNA cross-linked hydrogels[21]. Copyright 2011, American Chemical Society C) Schematic diagram of the construction of photothermally responsive MXene-DNA hydrogels and their application[27]. Copyright 2022, John Wiley and Sons |
图4 金属离子响应、氧化还原响应和酶响应型核酸水凝胶的应用。A)金属离子响应型纯DNA水凝胶的制备及金属离子检测原理[29]。B)铁3+的组装/铁2+-羧甲基纤维素(CMC)水凝胶和氧化还原触发的水凝胶的受控交联[31]。C)构建Cas9/sgRNA编辑的免疫检查点阻断DNA多核酸适配体水凝胶[35]。Fig. 4 Applications of metal-ion-responsive, redox-responsive, and enzyme-responsive nucleic acid hydrogels. A) Preparation of metal ion-responsive pure DNA hydrogels and the principle of metal ion detection[29]. Copyright 2021, Elsevier B) Assembly of Fe3+/controlled cross-linking of Fe2+-carboxymethylcellulose (CMC) hydrogels and redox-triggered hydrogels[31]. Copyright 2021, Elsevier C) Construction of Cas9/sgRNA-edited immune checkpoint-blocking DNA polynucleic acid aptamer hydrogels[35]. Copyright 2019, Elsevier |
图6 刺激响应核酸水凝胶在细胞治疗方面的应用。A)DSHV 系统诱导的宿主 APC 在体内募集和激活以产生强大的免疫反应和抗肿瘤作用的示意图[41]。B)光反应型核酸水凝胶用于肿瘤治疗的示意图[45]。C)多功能DNA敷料促进烧伤创面愈合的机制[48]。Fig. 6 Application of stimulus-responsive nucleic acid hydrogels in cell therapy. A) Schematic diagram of DSHV system-induced host APCs recruiting and activating in vivo to produce robust immune responses and antitumor effects[41]. Copyright 2018, American Chemical Society B) Schematic diagram of embedded photoreactive nucleic acid hydrogel for tumor treatment[45]. Copyright 2023, Springer Nature C) Mechanism of multifunctional DNA dressings to promote burn wound healing[48]. Copyright 2022, JohnWiley and Sons |
图7 核酸水凝胶在协同药物递送方面的应用。A)DNA-FKNa/Ag水凝胶修复MRSA感染伤口示意图[59]。B)miR-5590-SNA@DNAgel的制备和应用[66]。Fig. 7 Application of nucleic acid hydrogels in synergistic drug delivery. A) Schematic diagram of DNA-FKNa/Ag hydrogel repair of MRSA infected wound[59]. Copyright 2023, Elsevier B) Preparation and application of miR-5590- SNA@DNAgel[66]. Copyright 2023, Springer Nature |
表1 刺激响应型核酸水凝胶在生物医学方面的应用Table 1 Application of stimulus responsive nucleic acid hydrogel in biomedicine |
Areas of application | Type of stimulus | Principle of action | Ref |
---|---|---|---|
Cell imaging | Chemical trigger | ATP activates fluorescent signalling | 36 |
pH response | Fluorescent marker release | 37 | |
Cell therapy | Chemical trigger | CpG activates APC and the immune response | 40 |
ATP triggers the breakdown and release of CTCs | 41 | ||
Increased local ATP concentration and signalling early warning | 44 | ||
light response | Trigger Cell Photodynamic Therapy | 44 | |
pH, temperature response | Reacts specifically with the wound wound area | 48 | |
Drug delivery | light response | Delivery of cell-penetrating anticancer peptide drugs | 54 |
pH response | Loaded drug reaches the site of acidic pathology | 61 | |
chemical trigger | Specific sites encoding restriction endonucleases | 62 | |
Decomposed by biological enzymes in the body to release therapeutic drugs | 64 |
[1] |
|
[2] |
|
[3] |
|
[4] |
|
[5] |
|
[6] |
|
[7] |
|
[8] |
|
[9] |
|
[10] |
|
[11] |
|
[12] |
|
[13] |
(马翾, 张洋子, 许文涛. 生物技术进展, 2019, 9(6): 554.)
|
[14] |
|
[15] |
|
[16] |
|
[17] |
|
[18] |
|
[19] |
|
[20] |
|
[21] |
|
[22] |
(杨勃, 孙立梅, 潘玙璠, 董原辰, 孙亚伟, 刘冬生. 高分子学报, 2021, 52 (8):996.)
|
[23] |
|
[24] |
(程平, 张洋子, 马翾, 陈旭, 朱保庆, 许文涛. 中国生物工程杂志, 2020, 40 (3):132. )
|
[25] |
|
[26] |
|
[27] |
|
[28] |
|
[29] |
|
[30] |
|
[31] |
|
[32] |
|
[33] |
|
[34] |
|
[35] |
|
[36] |
|
[37] |
|
[38] |
|
[39] |
|
[40] |
|
[41] |
|
[42] |
|
[43] |
|
[44] |
|
[45] |
|
[46] |
|
[47] |
|
[48] |
|
[49] |
(潘国莹, 张吉傲笛, 梁永平, 郭保林. 四川大学学报(医学版), 2023, 54 (4):726.)
|
[50] |
|
[51] |
|
[52] |
|
[53] |
|
[54] |
|
[55] |
|
[56] |
|
[57] |
|
[58] |
|
[59] |
|
[60] |
|
[61] |
|
[62] |
|
[63] |
|
[64] |
|
[65] |
|
[66] |
|
[67] |
|
/
〈 |
|
〉 |