Spherically Directed Synthesis and Enhanced Cellular Internalization of Metal-Crosslinked DNA Micelles

Summary Using spherically directed reduction of metal ions, a facile and universal method for in situ crosslinking of DNA micelles is described. By incorporating a series of specific template domains into lipid-DNA monomers, copper-, silver-, and gold-crosslinked DNA micelles are formed. By combining characterization results and simulation algorithms, accurate structural profiling of DNA micelles is achieved for the first time. The prepared metal-crosslinked DNA micelles show obvious merits, including one-step formation of core structure and ligand corona, facile size tunability, monodispersity, stability against salt-induced aggregation, high utilization of DNA ligand, mild synthesis conditions, and less time consumption and better internalization. Based on our spherically directed synthesis, metal-crosslinked DNA micelle flares were further prepared for effective intracellular imaging by integrating an aptamer-toehold strategy. In addition, we extended the strategy to cholesterol-based double-stranded DNA micelles, giving strong evidence that our method is not only universal but also flexible.