Ho, M. S. M., Lim, A. Z. T., Ke, Y., Loh, W. W., Zheng, X. T., Yang, L., Dong, Z., Wang, F., Lim, J. Y. C., & Hu, Y. (2025). Cascade DNA Structural Transitions Enable Stimuli-Responsive Hydrogels. ACS Applied Materials Interfaces, 17(18), 27116–27125. https://doi.org/10.1021/acsami.5c01581
Abstract:
Cascade interactions are fundamental to enzyme catalysis and cellular activities, enabling dynamic and adaptive responses to environmental stimuli. DNA-based cascade systems have been widely employed to mimic biological processes, such as immune responses and DNAzyme catalysis, achieved mainly through the hybridization interaction. Herein, we present a cascade DNA system involving single-stranded sequences, noncanonical cofactor-bridged duplexes, and canonical duplexes to construct and dissociate hydrogel matrices. In this work, thymine-rich oligonucleotides (T-strands) exist as single-stranded random coils in a buffer at pH 7.2. Upon the introduction of a low-molecular-weight cofactor, melamine (MA), a supramolecular noncanonical configuration, termed the T-MA-T duplex, is formed. Subsequent addition of adenine-rich oligonucleotides (A-strands) to the system leads to the replacement of MA cofactors and the formation of more energetically favorable canonical A-T duplex structures. These consecutive structural transitions are further utilized as dynamic bridging elements in stimuli-responsive DNA hydrogels, facilitating liquid–hydrogel–liquid phase transitions. Moreover, we demonstrate precisely controlled release profiles of doxorubicin from the DNA hydrogel. This approach, leveraging both noncanonical and canonical DNA configurations in triggered cascade structural transitions, opens avenues for developing molecular switches, electronic nanodevices, adaptive materials, and other advanced applications.
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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 Agency for Science, Technology and Research, Science and Engineering Research Council - Central Research Fund, Use-Inspired Basic Research
Grant Reference no. : KIMR220901aSERCRF
This research / project is supported by the Agency for Science, Technology and Research - Manufacturing, Trade, and Connectivity Programmatic Fund
Grant Reference no. : M24M9b0013