Multi-dimensional DNA nanostructures isothermally assembled in hydrated ionic liquids
- 1University at Albany, State University of New York
Abstract
DNA nanostructures can be tailored to perform a wide variety of functions, with continued interest in biological applications. Some aspects of DNA nanostructure assembly can hinder the ability of nanostructures to be useful in physiological environments. Typical assembly methods employ magnesium ions to stabilize the structure, which leave the structure susceptible to damage by nucleases in body fluids. Further, DNA nanostructure assembly typically involves a thermal annealing protocol in which DNA strands are heated in a specific buffer to a high temperature and cooled slowly at specific rates, preventing convenient encapsulation of temperature-sensitive guest molecules. In this work, we demonstrate the assembly of a wide variety of DNA nanostructures and 3D crystals in a hydrated ionic liquid (choline dihydrogen phosphate, CDHP) instead of magnesium at constant moderate temperatures, thus avoiding thermal annealing. CDHP-assembled structures show enhanced biostability against a variety of nucleases. Molecular dynamics simulations show that choline ions stabilize DNA nanostructures by a direct and close-range interaction in contrast to the predominantly water-mediated interactions of Mg2+, leading to enhanced nuclease resistance in CDHP-containing environments. CDHP-assembled structures do not affect the viability of HepG2 cells and show higher cell internalization. Overall, this work develops a potential method to construct more biostable DNA nanostructures and 3D crystals in a simple one pot process. Assembly of DNA nanostructures under isothermal conditions is desirable for scaffolding biomolecules and to reduce the need for thermal annealing instruments, allowing nanostructure preparation in low-resource settings.
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BibTeX
@misc{talbot2026multidimensional,
title = {{Multi-dimensional DNA nanostructures isothermally assembled in hydrated ionic liquids}},
author = {H. Talbot and L. Nguyen and D. Gandavadi and Z. Nowzari and C. Mathur and G. Gallagher and K. Mongin and S. Vangaveti and T. J. Begley and X. Wang and A. R. Chandrasekaran},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.744742},
url = {https://www.biorxiv.org/content/10.64898/2026.09.02.744742v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Multi-dimensional DNA nanostructures isothermally assembled in hydrated ionic liquids
AU - H. Talbot
AU - L. Nguyen
AU - D. Gandavadi
AU - Z. Nowzari
AU - C. Mathur
AU - G. Gallagher
AU - K. Mongin
AU - S. Vangaveti
AU - T. J. Begley
AU - X. Wang
AU - A. R. Chandrasekaran
PY - 2026
DA - 2026/09/02
PB - bioRxiv
DO - 10.64898/2026.09.02.744742
UR - https://www.biorxiv.org/content/10.64898/2026.09.02.744742v1
AB - DNA nanostructures can be tailored to perform a wide variety of functions, with continued interest in biological applications. Some aspects of DNA nanostructure assembly can hinder the ability of nanostructures to be useful in physiological environments. Typical assembly methods employ magnesium ions to stabilize the structure, which leave the structure susceptible to damage by nucleases in body fluids. Further, DNA nanostructure assembly typically involves a thermal annealing protocol in which DNA strands are heated in a specific buffer to a high temperature and cooled slowly at specific rates, preventing convenient encapsulation of temperature-sensitive guest molecules. In this work, we demonstrate the assembly of a wide variety of DNA nanostructures and 3D crystals in a hydrated ionic liquid (choline dihydrogen phosphate, CDHP) instead of magnesium at constant moderate temperatures, thus avoiding thermal annealing. CDHP-assembled structures show enhanced biostability against a variety of nucleases. Molecular dynamics simulations show that choline ions stabilize DNA nanostructures by a direct and close-range interaction in contrast to the predominantly water-mediated interactions of Mg2+, leading to enhanced nuclease resistance in CDHP-containing environments. CDHP-assembled structures do not affect the viability of HepG2 cells and show higher cell internalization. Overall, this work develops a potential method to construct more biostable DNA nanostructures and 3D crystals in a simple one pot process. Assembly of DNA nanostructures under isothermal conditions is desirable for scaffolding biomolecules and to reduce the need for thermal annealing instruments, allowing nanostructure preparation in low-resource settings.
ER -