Responsive DNA-based hydrogels and their applications

Abstract

The term hydrogel describes a type of soft and wet material formed by cross-linked hydrophilic polymers. The distinct feature of hydrogels is their ability to absorb a large amount of water and swell. The properties of a hydrogel are usually determined by the chemical properties of their constituent polymer(s). However, a group of hydrogels, called "smart hydrogels," changes properties in response to environmental changes or external stimuli. Recently, DNA or DNA-inspired responsive hydrogels have attracted considerable attention in construction of smart hydrogels because of the intrinsic advantages of DNA. As a biological polymer, DNA is hydrophilic, biocompatible, and highly programmable by Watson-Crick base pairing. DNA can form a hydrogel by itself under certain conditions, and it can also be incorporated into synthetic polymers to form DNA-hybrid hydrogels. Functional DNAs, such as aptamers and DNAzymes, provide additional molecular recognition capabilities and versatility. In this Review, DNA-based hydrogels are discussed in terms of their stimulus response, as well as their applications.

Keywords: DNA; biological applications of polymers; hydrogels; responsive.

Figure 1

DNA hydrogel response to temperature and ions. a) Hydrogel dissolution at high temperature. b) Metal ions induced DNAyzme activity, resulting in gel-to-sol transition. c) AuNPs entrapped inside the gel. The upper buffer solution is initially colorless, but when the gel dissolves, the AuNPs are released to the solution, giving it a uniform red color.

Figure 2

DNA hydrogel response to molecules and photons. a) Hydrogel crosslinked by a DNA sequence containing adenosine-binding aptamer is converted to the sol phase by adenosine. b) Gel-to-sol transition induced by addition of the tetracycline. c) cDNA induced hydrogel volume change. d) Hydrogel phase transition regulated by UV/Vis irradiation.

Figure 3

DNA hydrogels as sensors. a) Visual detection of cocaine using a hydrogel with an enzymatic signal amplification step. Amylase is released only when cocaine is in the system, which can digest amylose and decrease the intensity of the blue amylose/iodine color. b) Transparent DNA hydrogel changes to red color in the presence of the target DNA. Addition of Ag⁺, along with a reducing reagent, can increase the sensitivity of DNA detection. c) Detection of mecury ions with a DNA staining dye, SYBR Green I. The dye binds to extended ssDNA, producing a yellow color. When DNA folds into a hairpin structure in the presence of Hg²⁺ ions, the dye emits green fluorescence. d) Hydrogel volume change caused by DNA strands can be measured using an optical fiber.

Figure 4

DNA hydrogels for separation and controlled release. a) DNA hydrogels can be used to capture and purify small molecules. A linker DNA strand containing an aptamer moiety can capture target molecules. Addition of polymer-DNA forms a hydrogel with the linker DNA and traps target molecules inside hydrogel. After washing, target molecules can be released by cDNA strands. b) Proteins bound to aptamer-coated beads are trapped inside a hydrogel. Addition of cDNA can release proteins from the hydrogel.