Dendrimer-like Hierarchical Framework Nucleic Acid for Real-Time Imaging of Intracellular Trafficking

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.