Multiple endocytic pathways operate on the plasma membrane of cells at any moment with diverse but specific cellular functions. Knowledge of uptake of synthetic nanoparticles and ligands with respect to endocytic pathways is crucial to device the appropriate ligands for therapeutic delivery into differentiated neurons for targeting neuronal diseases. We herein explore the mechanisms of cellular uptake of 3D tetrahedral DNA nanocages at different stages of differentiating neurons. We monitored the uptake, kinetics, and dynamics of DNA cages of different geometries, and interestingly we find a specific pattern and adaptability of the uptake of DNA devices with respect to the geometry of the ligand and specific endocytic pathways. We find that tetrahedral DNA nanocages get endocytosed mostly via clathrin-mediated endocytosis in fully mature neurons. This endocytic uptake and intracellular choreography of DNA nanodevices will help us design the smartly targeted biotherapeutics for targeting neuronal disorders.

Spatiotemporal Dynamics of Endocytic Pathways Adapted by Small DNA Nanocages in Model Neuroblastoma Cell-Derived Differentiated Neurons