Issue 5, 2017

pH- and ligand-induced release of loads from DNA–acrylamide hydrogel microcapsules


Herein, a method to construct stimuli-responsive DNA–acrylamide-based hydrogel microcapsules has been presented. This method involves the use of polyacrylamide chains modified with predesigned nucleic acid hairpin units and optionally single-strand tethers that provide the required hybridization and recognition functions to yield substrate-loaded stimuli-responsive hydrogel-based microcapsules. The synthesis of the microcapsules involves the loading of CaCO3 microparticles with the respective load substrates and the functionalization of the CaCO3 template particles with nucleic acid promoter units. In the presence of the hairpin-modified acrylamide chains, the promoter units induce the hybridization chain reaction (HCR), which leads to the formation of a hydrogel coating, which, after the dissociation of the CaCO3 cores, yields substrate-loaded stimuli-responsive hydrogel microcapsules. One of the microcapsule systems includes, in the hairpin-modified acrylamide constructs, and in the subsequent HCR-generated hydrogel shells, the caged sequences of anti-ATP or anti-cocaine aptamers. In the presence of ATP or cocaine, the duplex-caged aptamer sequences are separated via the formation of ATP- or cocaine–aptamer complexes, which results in the partial separation of the microcapsules and the release of the loads. The second type of microcapsule is cooperatively stabilized by bridges generated by HCR and pH-sensitive duplex units. Under acidic conditions, the pH-sensitive bridges dissociate via the formation of i-motif structures, which results in an increase in the fluidity of the microcapsule shells and the release of the loads. Preliminary studies indicate that ATP- or pH-responsive microcapsules loaded with the anticancer drug, doxorubicin, have a selective cytotoxic effect on MDA-MB-231 cancer cells.

Graphical abstract: pH- and ligand-induced release of loads from DNA–acrylamide hydrogel microcapsules

Supplementary files

Article information

Article type
Edge Article
27 Oct 2016
04 Jan 2017
First published
10 Jan 2017
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2017,8, 3362-3373

pH- and ligand-induced release of loads from DNA–acrylamide hydrogel microcapsules

W. Liao, S. Lilienthal, J. S. Kahn, M. Riutin, Y. S. Sohn, R. Nechushtai and I. Willner, Chem. Sci., 2017, 8, 3362 DOI: 10.1039/C6SC04770J

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