Hierarchically Structured DNA‐Based Hydrogels Exhibiting Enhanced Enzyme‐Responsive and Mechanical Properties

Abstract

Programmable stimuli‐responsive materials have great potential in biosensing and biomedical applications. However, the slow response of DNA hydrogels to biological targets, especially bio‐macromolecules, i.e., proteins, due to the slow mass transfer within hydrogel matrices, as well as poor mechanical strength, severely hinders their extensive applications. Herein, the construction of hierarchically structured DNA hydrogels exhibiting significantly enhanced responsive and mechanical properties via a facile cryostructuration process is demonstrated. During the cryostructuration, interconnected macropores that can function as the channels for the migration of bio‐macromolecular substances, i.e., enzymes, are formed with the generated ice crystals as templates; meanwhile, densely crosslinked networks between the macropores are formed by the concentrated monomers localized in the unfrozen zones of the gelation system, leading to higher strength of the gel matrices. By programming the sequences of the DNA crosslinkers, two model hydrogels composed of enzyme‐responsive DNA structures and catalytic DNA crosslinking structures that can collaborate with enzymes to form biocatalytic cascades are constructed, and, in both systems, the hierarchically structured DNA hydrogels exhibit significantly enhanced responsive properties and mechanical strengths compared with typical DNA hydrogels. Moreover, the introduction of thermosensitive polymers can further endow the system with thermally switchable responsive properties.

Engineered extracellular vesicles as intelligent nanosystems for next-generation nanomedicine

“…[237][238][239][240] Due to the specificity of enzymes to their substrates, a promising antitumor strategy is to design enzyme-triggered stimuli-responsive nanomaterials, which can more accurately identify tumor tissue, allowing more drugs to be concentrated at the primary site of the tumor, improving treatment effectiveness and reducing systemic toxicity. [241][242][243][244][245] Although the effect of the enzyme stimuli-responsive system in tumor therapy has been demonstrated for several years, 247 little attention has been paid to the construction of EV-based enzyme-responsive nanomaterials. Recently, enzyme-responsive nano-platforms with liposomes as carriers were reported.…”

DNA nanostructure-based nucleic acid probes: construction and biological applications

“…Conventional DNA hydrogels usually use polyacrylamide, poly (propylene oxide), or poly (N-isopropyl acrylamide) as backbones, functional DNAs (such as aptamers or DNAzyme) as crosslinkers. 95 To avoid the introduction of toxic reagents and improve the biocompatibility of hydrogels, pure DNA hydrogels have also been prepared via complementary base pairing using DNA nanostructures (e.g., T-, X-, and Y-shaped scaffold) as building blocks. 41 By changing the initial concentration of the DNA cross-linking agent, the size of DNA hydrogel can be finely tuned in the nanometer range, which is beneficial for intracellular transmission and imaging applications (Fig.…”

“…Conventional DNA hydrogels usually use polyacrylamide, poly(propylene oxide), or poly( N -isopropyl acrylamide) as the backbone, and functional DNAs (such as aptamers or DNAzymes) as crosslinkers. 95 To avoid the introduction of toxic reagents and improve the biocompatibility of hydrogels, pure DNA hydrogels have also been prepared via complementary base pairing using DNA nanostructures ( e.g. , T-, X-, and Y-shaped scaffolds) as building blocks.…”

Fast and Ample Light Controlled Actuation of Monodisperse All‐DNA Microgels

“…[ 29,30 ] Developing monodisperse all‐DNA microgels represents a crucial step to assemble exotic photonic superstructures [ 29,30 ] and embed them with responsive properties, [ 31 ] or produce hierarchical soft materials that can adapt and process signals. [ 32,33 ]…”

“…[29,30] Developing monodisperse all-DNA microgels represents a crucial step to assemble exotic photonic superstructures [29,30] and embed them with responsive properties, [31] or produce hierarchical soft materials that can adapt and process signals. [32,33] Beyond structural control, there is a growing interest to design responsive DNA. Owing to its great spatiotemporal capability, light is the most promising trigger for such a purpose.…”