Hu, Y., Liu, J., Ke, Y., Wang, B., Lim, J. Y. C., Dong, Z., Long, Y., & Willner, I. (2024). Oligo-Adenine and Cyanuric Acid Supramolecular DNA-Based Hydrogels Exhibiting Acid-Resistance and Physiological pH-Responsiveness. ACS Applied Materials & Interfaces, 16(22), 29235–29247. https://doi.org/10.1021/acsami.4c03834
Abstract:
Expanding the functions and applications of DNA by integrating noncanonical bases and structures into the biopolymer is a continuous scientific effort. An adenine-rich strand (A-strand) is introduced as functional scaffold revealing, in the presence of the low-molecular-weight cofactor cyanuric acid (CA, pKa 6.9), supramolecular hydrogel-forming efficacies demonstrating multiple pH-responsiveness. At pH 1.2, the A-strand transforms into a parallel A-motif duplex hydrogel crosslinked by AH+-H+A units due to the protonation of adenine (pKa 3.5). At pH 5.2, and in the presence of co-added CA, a helicene-like configuration is formed between adenine and protonated CA, generating a parallel A-CA triplex crosslinked hydrogel. At pH 8.0, the hydrogel undergoes transition into a liquid state, by deprotonation of CA cofactor units and disassembly of A-CA triplex into its constituent components. Density functional theory calculations and molecular dynamics simulations, supporting the structural reconfigurations of A-strand in the presence of CA, are performed. The sequential pH-stimulated hydrogel states are rheometrically characterized. The hydrogel framework is loaded with fluorescein-labeled insulin and the pH-stimulated release of insulin from the hydrogel across the pH barriers present in the gastrointestinal tract is demonstrated. The results provide principles for future application of the hydrogel for oral insulin administration for diabetes.
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Funding Info:
This research / project is supported by the Agency for Science, Technology and Research - Career Development Fund
Grant Reference no. : C210112014
This research / project is supported by the A*STAR Science and Engineering Research Council - SERC Central Research Fund UIBR
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This research is supported by core funding from: A*STAR Institute of Materials Research and Engineering (IMRE)
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This research / project is supported by the National Research Foundation, Singapore, and Agency for Science, Technology and Research - IAF-PP grant (OrBiTAl: Ocular Biomaterials for Vitreoretinal Therapeutic Applications)
Grant Reference no. : H20c6a0033
This research / project is supported by the National Research Foundation, Singapore, and Agency for Science, Technology and Research - Quantum Engineering Programme 2.0
Grant Reference no. : NRF2021-QEP2-03-P09