Department of Chemistry, McGill University, 801 Sherbrooke Street West, Montréal, Québec H3A 0B8, Canada.
ACS Nano. 2021 Mar 23;15(3):3631-3645. doi: 10.1021/acsnano.0c06136. Epub 2021 Feb 26.
DNA nanotechnology has produced a wide range of self-assembled structures, offering unmatched possibilities in terms of structural design. Because of their programmable assembly and precise control of size, shape, and function, DNA particles can be used for numerous biological applications, including imaging, sensing, and drug delivery. While the biocompatibility, programmability, and ease of synthesis of nucleic acids have rapidly made them attractive building blocks, many challenges remain to be addressed before using them in biological conditions. Enzymatic hydrolysis, low cellular uptake, immune cell recognition and degradation, and unclear biodistribution profiles are yet to be solved. Rigorous methodologies are needed to study, understand, and control the fate of self-assembled DNA structures in physiological conditions. In this review, we describe the current challenges faced by the field as well as recent successes, highlighting the potential to solve biology problems or develop smart drug delivery tools. We then propose an outlook to drive the translation of DNA constructs toward preclinical design. We particularly believe that a detailed understanding of the fate of DNA nanostructures within living organisms, achieved through thorough characterization, is the next required step to reach clinical maturity.
DNA 纳米技术已经产生了广泛的自组装结构，在结构设计方面提供了无与伦比的可能性。由于其可编程组装和对大小、形状和功能的精确控制，DNA 颗粒可用于许多生物应用，包括成像、传感和药物输送。尽管核酸的生物相容性、可编程性和易于合成已使其迅速成为有吸引力的构建块，但在生物条件下使用它们之前，仍有许多挑战需要解决。酶解、细胞摄取率低、免疫细胞识别和降解以及不清楚的生物分布特征仍有待解决。需要严格的方法学来研究、理解和控制自组装 DNA 结构在生理条件下的命运。在这篇综述中，我们描述了该领域目前面临的挑战以及最近的成功，强调了解决生物学问题或开发智能药物输送工具的潜力。然后，我们提出了一个展望，以推动 DNA 构建体向临床前设计的转化。我们特别认为，通过彻底的表征来深入了解 DNA 纳米结构在活生物体中的命运，是达到临床成熟所需的下一步。
