Department of Mechanical and Aerospace Engineering, Comprehensive Cancer Center, The Ohio State University Columbus, Columbus, OH, 43210, USA.
Department of Mechanical and Aerospace Engineering, The Ohio State University, Columbus, OH, 43210, USA.
Small. 2022 Jul;18(26):e2108063. doi: 10.1002/smll.202108063. Epub 2022 May 28.
DNA origami (DO) nanotechnology enables the construction of precise nanostructures capable of functionalization with small molecule drugs, nucleic acids, and proteins, suggesting a promising platform for biomedical applications. Despite the potential for drug and vaccine delivery, the impact of DO vehicles on immunogenicity in vivo is not well understood. Here, two DO vehicles, a flat triangle and a nanorod, at varying concentrations are evaluated in vitro and with a repeated dosing regimen administered at a high dose in vivo to study early and late immunogenicity. The studies show normal CD11b myeloid cell populations preferentially internalize DO in vitro. DO structures distribute well systemically in vivo, elicit a modest pro-inflammatory immune response that diminishes over time and are nontoxic as shown by weight, histopathology, lack of cytokine storm, and a complete biochemistry panel at the day 10 end point. The results take critical steps to characterize the biological response to DO and suggest that DO vehicles represent a promising platform for drug delivery and vaccine development where immunogenicity should be a key consideration.
DNA 折纸（DO）纳米技术能够构建精确的纳米结构，这些结构能够功能化小分子药物、核酸和蛋白质，这为生物医学应用提供了一个有前途的平台。尽管 DO 载体在药物和疫苗传递方面具有潜力，但它们在体内对免疫原性的影响还不是很清楚。在这里，两种 DO 载体，即平面三角形和纳米棒，在不同浓度下进行了体外评估，并在高剂量下进行了重复给药方案的体内研究，以研究早期和晚期的免疫原性。研究表明，正常的 CD11b 髓样细胞群在体外优先内化 DO。DO 结构在体内系统分布良好，引发适度的促炎免疫反应，随着时间的推移反应减弱，而且在第 10 天终点时，体重、组织病理学、细胞因子风暴缺失以及完整的生物化学指标均表明无毒。这些结果对 DO 的生物学反应进行了关键性的描述，并表明 DO 载体是药物传递和疫苗开发的一个有前途的平台，在这个平台中，免疫原性应该是一个关键的考虑因素。
