Tang Xinyue, Zhai Tingting, Li Tiancheng, Jin Yu, Lei Dantong, Zhu Cheng, Qu Luyao, Li Yingfu, Wang Yudong, Gu Hongzhou, Fang Bing
Department of Orthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology, Shanghai, 200011, China.
State Key Laboratory of Synergistic Chem-Bio Synthesis, Department of Chemical Biology, School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China.
J Nanobiotechnology. 2025 Sep 29;23(1):615. doi: 10.1186/s12951-025-03707-1.
Precise regulation of cellular functions is fundamental for advancing tissue regeneration and drug delivery systems. Structural DNA nanotechnology enables the design of well-defined nanostructures, emerging as a promising platform in these biomedical applications. However, a clear understanding of how the dimensional properties of DNA nanostructures affect cellular uptake and biological responses remains limited. In this study, we constructed three distinct DNA nanostructures: a one-dimensional six-helix bundle (6HB), a two-dimensional three-point star, and a three-dimensional tetrahedron. We systematically evaluated their endocytic efficiency in five representative cell types: endothelial cells, dermal fibroblasts, myoblasts, chondrocytes, and osteoblasts. Among them, the 6HB exhibited the highest cellular uptake, with minimal variability across cell types in both 2D petri dish cultures and 3D multicellular spheroid invasion models. Moreover, DNA nanostructures were found to enhance cell proliferation in fibroblasts and chondrocytes, support chondrocyte phenotype maintenance, and, in the case of the 6HB, promote myoblast differentiation. These findings provide new insights into structure-function relationships in DNA nanomaterials and offer guidance for optimizing DNA-based platforms for drug delivery and regenerative medicine.
细胞功能的精确调控对于推进组织再生和药物递送系统至关重要。结构DNA纳米技术能够设计出明确的纳米结构，在这些生物医学应用中成为一个有前景的平台。然而，对于DNA纳米结构的尺寸特性如何影响细胞摄取和生物学反应的清晰理解仍然有限。在本研究中，我们构建了三种不同的DNA纳米结构：一维六螺旋束（6HB）、二维三点星和三维四面体。我们系统地评估了它们在五种代表性细胞类型中的内吞效率：内皮细胞、真皮成纤维细胞、成肌细胞、软骨细胞和成骨细胞。其中，6HB表现出最高的细胞摄取率，在二维培养皿培养和三维多细胞球体侵袭模型中，不同细胞类型之间的变异性最小。此外，发现DNA纳米结构可增强成纤维细胞和软骨细胞的细胞增殖，支持软骨细胞表型维持，并且对于6HB而言，可促进成肌细胞分化。这些发现为DNA纳米材料的结构-功能关系提供了新的见解，并为优化基于DNA的药物递送和再生医学平台提供了指导。
