DNA nanostructures, known for their programmability, ease of modification, and favourable biocompatibility, have gained widespread application in the biomedical field. Among them, Tetrahedral DNA Origami (TDOs), as a novel DNA nanostructure, possesses well‐defined structures, multiple modification sites, and large cavities, making it a promising drug carrier. However, current understanding of TDOs' interactions with biological systems, particularly with target cells and organs, remains unexplored, limiting its further applications in biomedicine. In this work, we prepared TDOs with an average particle size of 40 nm and labelled them with Cy5 fluorescent molecules. Following intravenous injection in mice, the uptake of TDOs by different types of liver and kidney cells was observed. Results indicated that TDOs accumulate in renal tubules and are metabolized by Kupffer cells, epithelial cells, and hepatocytes in the liver. Additionally, in a tumour‐bearing mouse model, TDOs passively targeted tumour tissues and exhibited excellent tumour penetration and retention after rapid metabolism in hepatocytes. Our findings provide crucial insights for the development of TDO‐based drug delivery systems.

中文翻译：

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肿瘤中四面体 DNA 折纸的肝和肾细胞摄取和运输的可视化

DNA纳米结构以其可编程性、易于修饰和良好的生物相容性而闻名，在生物医学领域获得了广泛的应用。其中，四面体DNA折纸（TDOs）作为一种新型DNA纳米结构，具有明确的结构、多个修饰位点和大的空腔，使其成为一种有前途的药物载体。然而，目前对 TDO 与生物系统，特别是与靶细胞和器官相互作用的了解尚未得到探索，限制了其在生物医学中的进一步应用。在这项工作中，我们制备了平均粒径为40 nm的TDO，并用Cy5荧光分子标记它们。小鼠静脉注射后，观察到不同类型的肝和肾细胞对 TDO 的摄取。结果表明，TDO 在肾小管中积累，并由肝脏中的库普弗细胞、上皮细胞和肝细胞代谢。此外，在荷瘤小鼠模型中，TDO 被动靶向肿瘤组织，在肝细胞中快速代谢后表现出出色的肿瘤渗透性和保留性。我们的研究结果为基于 TDO 的药物输送系统的开发提供了重要的见解。