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Geometry of a DNA Nanostructure Influences Its Endocytosis: Cellular Study on 2D, 3D, and in Vivo Systems
ACS Nano ( IF 15.8 ) Pub Date : 2022-06-17 , DOI: 10.1021/acsnano.2c01382
Anjali Rajwar 1 , Shravani Reddy Shetty 2 , Payal Vaswani 1 , Vinod Morya 1 , Amlan Barai 3 , Shamik Sen 3 , Mahendra Sonawane 2 , Dhiraj Bhatia 1, 4
Affiliation  

Fabrication of nanoscale DNA devices to generate 3D nano-objects with precise control of shape, size, and presentation of ligands has shown tremendous potential for therapeutic applications. The interactions between the cell membrane and different topologies of 3D DNA nanostructures are crucial for designing efficient tools for interfacing DNA devices with biological systems. The practical applications of these DNA nanocages are still limited in cellular and biological systems owing to the limited understanding of their interaction with the cell membrane and endocytic pathway. The correlation between the geometry of DNA nanostructures and their internalization efficiency remains elusive. We investigated the influence of the shape and size of 3D DNA nanostructures on their cellular internalization efficiency. We found that one particular geometry, i.e., the tetrahedral shape, is more favored over other designed geometries for their cellular uptake in 2D and 3D cell models. This is also replicable for cellular processes like cell invasion assays in a 3D spheroid model, and passing the epithelial barriers in in vivo zebrafish model systems. Our work provides detailed information for the rational design of DNA nanodevices for their upcoming biological and biomedical applications.

中文翻译:

DNA 纳米结构的几何结构影响其内吞作用:2D、3D 和体内系统的细胞研究

制造纳米级 DNA 设备以生成 3D 纳米物体,并精确控制配体的形状、大小和呈现,显示出巨大的治疗应用潜力。细胞膜与 3D DNA 纳米结构的不同拓扑结构之间的相互作用对于设计用于将 DNA 设备与生物系统连接的有效工具至关重要。由于对它们与细胞膜和内吞途径的相互作用了解有限,这些 DNA 纳米笼的实际应用在细胞和生物系统中仍然受到限制。DNA 纳米结构的几何形状与其内化效率之间的相关性仍然难以捉摸。我们研究了 3D DNA 纳米结构的形状和大小对其细胞内化效率的影响。我们发现一个特定的几何形状,即,四面体形状比其他设计的几何形状更受青睐,因为它们在 2D 和 3D 细胞模型中的细胞摄取。这也适用于细胞过程,如 3D 球体模型中的细胞入侵检测,以及在体内斑马鱼模型系统中通过上皮屏障。我们的工作为 DNA 纳米器件的合理设计及其即将到来的生物学和生物医学应用提供了详细信息。
更新日期:2022-06-17
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