Flash Synthesis of Spherical Nucleic Acids with Record DNA Density

Nanoparticles (NPs) decorated with a high density of DNA strands, also known as spherical nucleic acids (SNAs), are widely used in DNA-programmable assembly, sensing, imaging, and therapeutics. A regular SNA synthesis is very time-consuming, which requires great caution to avoid NP aggregation. Herein we report an extremely simple, efficient, and scalable process to realize instant (in seconds) synthesis of SNAs with record-high DNA density. Our method relies on a rapid water removal from a DNA/NP mixture in contact with a butanol phase. This process generates a dehydrated "solid solution" that greatly accelerates DNA anchorage on NPs via Au–S bonding. Compared to a state-of-the-art DNA conjugation strategy in the literature, up to 3-time increase of DNA density is achieved by the instant dehydration in butanol (INDEBT). The ultradense DNA grafting is accomplished in a few seconds, which is highly hybridizable to form core–satellite assemblies. Our work turns SNA synthesis into an easy job, and enables future explorations of physical, chemical, and biological effects of SNAs with ultrahigh DNA density.