Freezing-induced solid-liquid microphase separation for self-assembly of functional nucleic acid nanoparticles
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Updated: Nov 10, 2026
Self-Assembly of Gamma-Modified Peptide Nucleic Acids into Complex Nanostructures in Organic Solvent Mixtures
Published on: June 26, 2020
Tao Zeng1,2,3, Jiahui Fang1, Jian Hao4,5
1New Cornerstone Science Laboratory, MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Key Laboratory of Analysis and Testing Technology for Food Safety and Health, College of Chemistry, Fuzhou University, Fuzhou, PR China.
Abstract:
In nature, nuclear DNA complexed with histone form highly condensed chromatin via loop extrusion and microphase separation, yielding physically constrained solid-like structures. Inspired by this natural compaction, here we demonstrate that freezing-induced crystallization pressure and freeze-concentration effects trigger solid-liquid microphase separation for efficient DNA compression. Freezing compress various nucleic acids (single stranded DNA, molecular beacons, siRNA, plasmid DNA) into high-density states that self-assemble into nanoparticles (DNA-NPs, MB-NPs, siBcl-2-NPs, siPLK1-NPs, pEGFP-NPs). Molecular dynamics simulations reveal that ice crystal growth increases solute concentration, enhancing DNA intermolecular interactions to form supramolecular chains. Stress at advancing ice-liquid interfaces further orders and compacts these supramolecular chains into nanoparticles. In breast cancer cells, MB-NPs detect miRNA-21; siBcl-2-NPs downregulate Bcl-2 protein; siPLK1-NPs exhibited antitumor effects; and pEGFP-NPs mediate green fluorescent protein (GFP) expression. This freeze-induced self-assembly strategy replaces chemical synthesis with physical constraints, establishing a versatile platform for facile production of nucleic acid nanoparticles.
