Advancing Spherical Nucleic Acid Synthesis in Less-Polar Solvents.

Yichen Ye,Meiyun Ye,Ziyue Guo,Y. Hao,Zhaoxiang Deng

Published 2025 in Small

ABSTRACT

Spherical nucleic acids (SNAs) are radially packed, highly dense DNA "forests" on nanoparticle cores, depicting a useful class of artificially engineered bionanomaterials. The widespread uses of SNAs in diverse chemistry and nanotechnology areas have driven their synthetic innovations toward reduced time/cost and ever-improved quality. Different from existing methods based on salt-aging, low-pH, freezing, and dehydration conditions, herein a speedy and facile way is reported to produce SNAs in miscible aqueous-alcoholic media with easily adjustable solvent polarities. Critically, it is discovered that the non-aqueous environment of a water/isopropanol (IPA) mixture plays a vital role in affecting DNA interaction with gold nanoparticles (AuNPs) via different surface-anchoring groups. In addition to significantly accelerated DNA conjugation on AuNPs, the IPA-based strategy achieves various unprecedented controls on the formation of SNAs. These unique features include enhanced DNA adsorption (and ligand desorption) on AuNPs and the possibility of using gold-alkyne linkage for a rapid SNA preparation. Highly efficient SNA syntheses are achieved based on unmodified, thiolated, and alkynated DNA. Moreover, solvent-programmed directionality control of DNA grafts on AuNPs is realized based on alkyne/phosphorothioate dual-functionalities, which is otherwise unrealizable. The high effectiveness of the IPA-based method points to a previously unconsidered microenvironment-related DNA-nanoparticle interaction for innovating SNA synthesis.

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