College of Chemistry and Materials Science, The Education Ministry Key Lab of Resource Chemistry, Joint International Research Laboratory of Resource Chemistry of Ministry of Education, Shanghai Key Laboratory of Rare Earth Functional Materials, and Shanghai Frontiers Science Center of Biomimetic Catalysis, Shanghai Normal University, Shanghai200234, China.
State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai200025, China.
ACS Appl Mater Interfaces. 2023 Jan 25;15(3):3839-3850. doi: 10.1021/acsami.2c20504. Epub 2023 Jan 13.
Framework nucleic acids (FNAs) represent a new type of DNA-based nanomaterials and possess great potentials in biosensing, bioimaging, and molecular delivery. Hierarchical DNA nanostructures that consist of multiple FNA monomers increase the capacity for drug delivery and multifunctional modification. However, there are relatively few studies devoted to the behavior and regulation of hierarchical FNAs in living cells, impeding their further applications. Herein, we constructed a dendritic nanostructure with five tetrahedral DNA nanocages and characterized the real-time internalization, inter-organelle trafficking, and exocytosis in living mammalian cells. In comparison to FNA monomers, FNA dendrimers exhibit increased endocytosis and prolonged cellular retention. Single-particle tracking on hundreds of FNA dendrimers exhibits no interference on the mobility or kinetics of subcellular organelles, implying that FNAs as well as their higher-order derivatives are ideal intracellular imaging probes and nanocarriers. Our study validates the suitability and superiority of hierarchical DNA nanostructures as high-valency scaffolds for biomedical applications.
框架核酸 (FNAs) 代表了一种新型的基于 DNA 的纳米材料，在生物传感、生物成像和分子传递方面具有巨大的潜力。由多个 FNA 单体组成的分级 DNA 纳米结构增加了药物传递和多功能修饰的能力。然而，很少有研究致力于研究分级 FNAs 在活细胞中的行为和调控，这阻碍了它们的进一步应用。在此，我们构建了一个具有五个四面体形 DNA 纳米笼的树枝状纳米结构，并在活哺乳动物细胞中对其进行了实时内化、细胞器间运输和胞吐作用的表征。与 FNA 单体相比，FNA 树突状聚合物表现出更高的内吞作用和更长的细胞保留时间。对数百个 FNA 树突状聚合物的单颗粒跟踪显示，对亚细胞细胞器的迁移率或动力学没有干扰，这意味着 FNAs 及其更高阶衍生物是理想的细胞内成像探针和纳米载体。我们的研究验证了分级 DNA 纳米结构作为生物医学应用的高价支架的适用性和优越性。
