Evaporative Drying: A General and Readily Scalable Route to Spherical Nucleic Acids with Quantitative, Fully Tunable, and Record‐High DNA Loading

Nanoparticles (NPs) grafted with highly dense DNA strands are termed as spherical nucleic acids (SNAs), which have important applications benefiting from various unique properties unpossessed by naturally occurring nucleic acids. To overcome existing challenges toward an ideal SNA synthesis, herein, a very simple, while highly effective evaporative drying strategy featuring various long-desired advantages, is reported. This includes record-high DNA loading, generality for more NP materials, fully and quantitatively tunable DNA density, and readiness toward bulk production. The process requires almost zero care and the solid products are especially suitable for a long-time storage without quality degradation. The research reveals a quick and highly efficient packing of thiol-tagged DNA on the NP surface at the critical moment of drying, which refreshes previous knowledge on DNA conjugation chemistry. Based on this advancement, practical applications of SNAs in various fields may become possible.