Cationic lipid modification of DNA tetrahedral nanocages enhances their cellular uptake

Self-assembled DNA nanocages are among the most promising candidates for bioimaging and payload delivery into cells. DNA nanocages have great potential to efficiently address drug resistance and nucleic acid delivery problems due to precise control of their shape and size, and excellent biocompatibility. Although DNA nanostructures demonstrate some cellular uptake, because they bear a highly negative charge, the uptake of tetrahedral nanostructures is hindered by electrostatic repulsion. In this study, we describe a method to enhance the cellular uptake of DNA nanostructures using a binary system containing DNA and a positively charged head group with a hydrophobic lipid chain containing lipids for cellular internalization. Here we represent the functionalization of a model cage, DNA tetrahedron (TD) with a cationic lipid, N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA). Atomic force microscopy (AFM) and other standard characterization techniques were used to explore the co-assembly of the DNA tetrahedron and DOTMA. We revealed a simple confocal microscopy-based approach to show the enhancement in the cellular uptake of DNA nanocages. This new method will find multiple applications in delivery applications such as gene transfection, drug delivery and targeted bioimaging.