Design and application of stimuli-responsive DNA hydrogels: A review

Abstract

Deoxyribonucleic acid (DNA) hydrogels combine the properties of DNAs and hydrogels, and adding functionalized DNAs is key to the wide application of DNA hydrogels. In stimuli-responsive DNA hydrogels, the DNA transcends its application in genetics and bridges the gap between different fields. Specifically, the DNA acts as both an information carrier and a bridge in constructing DNA hydrogels. The programmability and biocompatibility of DNA hydrogel make it change macroscopically in response to a variety of stimuli. In order to meet the needs of different scenarios, DNA hydrogels were also designed into microcapsules, beads, membranes, microneedle patches, and other forms. In this study, the stimuli were classified into single biological and non-biological stimuli and composite stimuli. Stimuli-responsive DNA hydrogels from the past five years were summarized, including but not limited to their design and application, in particular logic gate pathways and signal amplification mechanisms. Stimuli-responsive DNA hydrogels have been applied to fields such as sensing, nanorobots, information carriers, controlled drug release, and disease treatment. Different potential applications and the developmental pro-spects of stimuli-responsive DNA hydrogels were discussed.

Keywords: Biological stimuli; Composite stimuli; DNA hydrogel; Non-biological stimuli; Stimuli-responsive.

Graphical abstract

Fig. 1

(A) Synthesis of DNAzyme-triggered Zn²⁺-responsive DNA hydrogel. Copyright 2021, American Chemical Society. (B) Schematic of mRNA delivery by pH-responsive DNA nano-hydrogel, (a) Schematic of the “X”-shaped DNA scaffold, (b) Structural changes of the pH-responsive Itail and Icap, and (c) DNA nano-hydrogel-assisted mRNA delivery and its intracellular pH-responsive release. Copyright 2021, Wiley-VCH. (C) Preparation of pH-responsive DNA hydrogel by RCA method; the I-motif structure was destroyed when pH changed from 5.0 to 8.0. Copyright 2017, Wiley-VCH. (D) Composite diagram of pH-responsive smart bilayer DNA hydrogel film actuators; the actuators deform reversibly when the pH changes. Copyright 2020, Wiley-VCH. (E) Schematic of pH-controlled self-assembly DNA hydrogel. (a) “Y”-shaped DNA scaffolds synthesize DNA when pH is 7, (b) DNA hydrogel dissociated under acidic conditions, and (c) Gel state and liquid state of DNA hydrogel. Copyright 2018, The Royal Society of Chemistry.

Fig. 2

(A) Scheme of light-induced shape-memory transition from glucosamine borate ester bridge and trans azobenzene stabilized double crosslinking agent hydrogel. Copyright 2019, The Royal Society of Chemistry. (B) (a) Scheme of photoisomerization between DTEo and DTEc. (b) Schematic of preparation and light-induced shape-memory properties of DNA hydrogel. Copyright 2018, American Chemical Society. (C) Carbon dot-DNA-protoporphyrin hybrid hydrogel for sustained photoinduced antimicrobial activity. Copyright 2019, Elsevier. (D) Conceptual illustration of the photolithographic formation of shape-controlled DNA-motif hydrogels based on the photo-activated self-assembly of DNA nanostructures. Copyright 2019, American Institute of Physics. (E) Schematic of injectable and NIR-Responsive DNA–Inorganic Hybrid Hydrogels. Copyright 2020, Wiley-VCH.

Fig. 3

Schematic of magnetic driven DNA hydrogel synthesis. (A) Enzymatic amplification of RCA to produce ultralong DNA strand products. (B) Permanent crosslinking and dynamic crosslinking. Green strands represent the DNA chain product of secondary amplification. (C) Schematic of the behavior of a robot when it strikes and passes through an obstacle. (D) The characterization of shape adaptability of the DNA robot. Copyright 2019, Wiley-VCH.

Fig. 4

(A) (a) Schematic of target-switchable DNA hydrogels coupled with a Bi₂Sn₂O₇/Bi₂S₃ heterojunction based on in situ anion exchange for photoelectrochemical detection of DNA. (b) PEC response of sensor to different target concentrations. Copyright 2021, The Royal Society of Chemistry. (B) (a) Schematic of imaging ellipsometry biosensor based on DNA hydrogelation for multiplexed exosomal miRNA detection. (b) Linear range of the IES for the multiplexed detection of let-7a, miR-375, and miR-21. Copyright 2020, American Chemical Society. C. Schematic of the electrochemical biosensing platform based on hybrid DNA hydrogel using for miR-21detection. Copyright 2018, Elsevier. (D) (a) Schematic of target miRNA 155-Induced Duplex-Specific Nuclease Signal Amplification Possess, (b) schematic of SERS Platform construction, and (c) preparation of TB Trapped 3D DNA Hydrogel. Copyright 2017, American Chemical Society.

Fig. 5

Schematic of the principle of a dynamically programmed DNA hydrogel based on a DNA circuit system through cascading toehold-mediated DNA displacement reactions (TMDRs). Copyright 2019, Wiley-VCH.

Fig. 6

(A) Schematic of carboxymethyl cellulose (CMC) stimuli-responsive nucleic acid-based hydrogel microcapsule system. Copyright 2020, American Chemical Society. (B) Schematic of the liposome–DNA hydrogel and its stimuli-responsive release behavior. Copyright 2018, Wiley-VCH. (C) Molecular design and synthesis route of DNA/DEX-g-DOPA hydrogel. (a) Synthesis route of DEX-g-DOPA. (b) Preparation of nanofiber-assembled hydrogel with volumetric responsiveness upon solvent polarity. (c) Electric circuit switched by a microbial metabolism process which produced ethanol using DNA/DEX-g-DOPA hydrogel as dynamic wires. Copyright 2020, Wiley-VCH. (D) Schematic of ion channel preparation process based on DNA hydrogel. Copyright 2018, Wiley-VCH. (E) Laser-patterning demonstrations of in situ assembly of DNA supramolecular Photonic hydrogels. Copyright 2021, American Chemical Society.