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基于滚环扩增产物的纯核酸纳米结构的构建及其在生物医学中的应用。

Construction of rolling circle amplification products-based pure nucleic acid nanostructures for biomedical applications.

机构信息

Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, 1 Ningde Road, Qingdao 266073, China.

出版信息

Acta Biomater. 2023 Apr 1;160:1-13. doi: 10.1016/j.actbio.2023.02.005. Epub 2023 Feb 9.

DOI:10.1016/j.actbio.2023.02.005
PMID:36764595
Abstract

Nucleic acid nanomaterials with good biocompatibility, biodegradability, and programmability have important applications in biomedical field. Nucleic acid nanomaterials are usually combined with some inorganic nanomaterials to improve their biological stability. However, undefined toxic side effects of composite nanocarriers hamper their application in vivo. As a nanotool capable of avoiding potential biotoxicity, nanostructures composed entirely of DNA oligonucleotides have been rapidly developed in the field of biomedicine in recent years. Rolling circle amplification (RCA) is an isothermal enzymatic nucleic acid amplification technology for large-scale production of periodic DNA/RNA with pre-designed desirable structures and functions. RCA products with different functional parts can be customized by changing the sequence of the circular template, thereby generating complex multifunctional DNA nanostructures, such as DNA nanowire, nanoflower, origami, nanotube, nanoribbon, etc. More importantly, RCA products as nonnicked building blocks can enhance the biostability of DNA nanostructures, especially in vivo. These RCA products-based nucleic acid nanostructures can be used as scaffolds or nanocarriers to interact or load with metal nanoparticles, proteins, lipids, cationic polymers, therapeutic nucleic acids or drugs, etc. This paper reviews the assembly strategies of RCA based DNA nanostructures with different shape and their applications in biosensing, bioimaging and biomedicine. Finally, the development prospects of the nucleic acid nanomaterials in clinical diagnosis and treatment of diseases are described. STATEMENT OF SIGNIFICANCE: As a nanotool capable of avoiding potential biotoxicity, nanostructures composed entirely of DNA oligonucleotides have been rapidly developed in the field of biomedicine in recent years. Rolling circle amplification (RCA) is an isothermal enzymatic nucleic acid amplification technology for large-scale production of periodic DNA/RNA with pre-designed desirable structures and functions. This paper reviews the construction of various shapes of pure nucleic acid nanomaterials based on RCA products and their applications in biosensing, bioimaging and biomedicine. This will promote the development of biocompatible DNA nanovehicles and their further application in living systems, including bioimaging, molecular detection, disease diagnosis and drug delivery, finally producing a significant impact in the field of nanotechnology and nanomedicine.

摘要

具有良好生物相容性、生物可降解性和可编程性的核酸纳米材料在生物医学领域有重要应用。核酸纳米材料通常与一些无机纳米材料结合使用,以提高其生物稳定性。然而,复合纳米载体未定义的毒性副作用阻碍了它们在体内的应用。作为一种能够避免潜在生物毒性的纳米工具,近年来完全由 DNA 寡核苷酸组成的纳米结构在生物医学领域得到了迅速发展。滚环扩增(RCA)是一种等温酶促核酸扩增技术,可大规模生产具有预设计理想结构和功能的周期性 DNA/RNA。通过改变环形模板的序列,可以定制具有不同功能部分的 RCA 产物,从而产生复杂的多功能 DNA 纳米结构,如 DNA 纳米线、纳米花、折纸、纳米管、纳米带等。更重要的是,RCA 产物作为无切口的构建块可以增强 DNA 纳米结构的生物稳定性,特别是在体内。这些基于 RCA 产物的核酸纳米结构可用作支架或纳米载体,与金属纳米粒子、蛋白质、脂质、阳离子聚合物、治疗性核酸或药物等相互作用或负载。本文综述了不同形状的 RCA 基 DNA 纳米结构的组装策略及其在生物传感、生物成像和生物医学中的应用。最后,描述了核酸纳米材料在疾病临床诊断和治疗中的发展前景。

意义声明

作为一种能够避免潜在生物毒性的纳米工具,近年来完全由 DNA 寡核苷酸组成的纳米结构在生物医学领域得到了迅速发展。滚环扩增(RCA)是一种等温酶促核酸扩增技术,可大规模生产具有预设计理想结构和功能的周期性 DNA/RNA。本文综述了基于 RCA 产物构建的各种形状的纯核酸纳米材料的方法及其在生物传感、生物成像和生物医学中的应用。这将促进生物相容性 DNA 纳米载体的发展及其在包括生物成像、分子检测、疾病诊断和药物输送在内的活体系统中的进一步应用,最终在纳米技术和纳米医学领域产生重大影响。

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