Shape-dependent cell entry and intracellular transport of self-assembled DNA nanostructures

  Plasma membranes form the first interface for cell entry of particles in cell communications, viral infection or drug delivery. Extensive studies on endocytosis and intracellular trafficking of these naturally existing or artificial particles have led to the discovery of novel drugs and the design of drug delivery carriers. More recent attention has been drawn toward the cell entry of self-assembled DNA nanostructures. Whereas DNA is typically impermeable to the plasma membrane due to its polyanionic nature, several types of DNA nanostructures show efficient cellular uptake in the absence of transfection agents. These new findings open new opportunities for constructing intelligent cargo delivery systems from these biocompatible, nonviral DNA nanocarriers. However, how the morphology of DNA nanostructures affects their interactions with cells remains largely elusive. 

  In this talk, I will present a set of our recent studies on shape-dependent cell entry and intracellular traffic of self-assembled DNA nanostructures. 1) We investigated the endocytotic internalization and subsequent transport of tetrahedral DNA nanostructures by mammalian cells through single-particle tracking and biochemical experiments; 2) We performed molecular dynamics to reveal the underlying mechanism for cell entry; 3) We studied the effects of size, shape and dimension of DNA nanostructures on the efficiency of cell entry. These studies improve our understanding of the entry into cells and transport pathways of DNA nanostructures, which also form the basis for designing DNA-nanostructure-based drug delivery nanocarriers for targeted therapy.