Single and Bilayer Polyacrylamide Hydrogel-Based Microcapsules for the Triggered Release of Loads, Logic Gate Operations, and Intercommunication between Microcapsules

A method to assemble loaded stimuli-responsive DNA-polyacrylamide hydrogel-stabilized microcapsules is presented. The method involves coating substrate-loaded CaCO₃ microparticles, functionalized with nucleic acid promoter units, and cross-linking DNA-modified polyacrylamide chains on the microcapsules, using the hybridization chain reaction (HCR) to yield the DNA-cross-linked hydrogel coating. Dissolution of the CaCO₃ particles generated the substrate-loaded hydrogel-protected microcapsules. The microcapsule-hydrogel shells include engineered stimuli-responsive oligonucleotide cross-linkers that control the stiffness of the hydrogel shells, allowing the triggered release of the loads. One approach includes the incorporation of cofactor-dependent DNAzyme units into the cross-linked hydrogel layers (cofactor = Mg²⁺ ions, Zn²⁺ ions, or histidine) as stimuli-responsive units. Cleavage of the cross-linking DNAzyme substrates by the respective cofactors yields hydrogel coatings with a reduced stiffness and higher porosity that allow the release of the loads. A further approach involved the application of the HCR process to assemble the bilayer hydrogel microcapsules that are unlocked by two cooperative triggers. Bilayer microcapsules consisting of a K⁺ ions-stabilized G-quadruplex/18-crown-6-ether (CE) responsive layer and a Mg²⁺ ion DNAzyme-responsive layers are presented. Unlocking and locking of the G-quadruplex cross-linked layer by 18-crown-6-ether and K⁺ ions, respectively, in the presence of Mg²⁺ ions allow the switchable controlled release of the load. In addition, the intercommunication of two kinds of stimuli-responsive bilayer hydrogel microcapsules carrying two different loads (tetramethylrhodamine-dextran, TMR-D, and CdSe/ZnS quantum dots) is demonstrated. The intercommunication process involves the stimuli-triggered generation of "information transfer" strands from one microcapsule to another that activate the release of the loads.