Fluorocarbon-DNA Conjugates for Enhanced Cellular Delivery: Formation of a Densely Packed DNA Nano-Assembly

Forming nano-assemblies is essential for delivering DNA conjugates into cells, with the DNA density in the nano-assembly playing an important role in determining the uptake efficiency. In this study, we developed a strategy for the facile synthesis of DNA strands bearing perfluoroalkyl (R_F) groups (R_F-DNA conjugates) and investigated how they affect cellular uptake. An R_F-DNA conjugate bearing a long R_F group at the DNA terminus forms a nano-assembly with a high DNA density, which results in greatly enhanced cellular uptake. The uptake mechanism is mediated by clathrin-dependent endocytosis. The use of R_F groups to densely assemble negatively charged DNA is a useful strategy for designing drug delivery carriers.