Flash Synthesis of Spherical Nucleic Acids with Record DNA Density

J Am Chem Soc. 2021 Mar 3;143(8):3065-3069. doi: 10.1021/jacs.1c00568. Epub 2021 Feb 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemistry Techniques, Synthetic
  • DNA / chemical synthesis*
  • DNA / chemistry*
  • Kinetics
  • Nanoparticles / chemistry*

Substances

  • DNA