Self‐Assembled DNA Hydrogels with Designable Thermal and Enzymatic Responsiveness

Abstract

DNA has received considerable attention as a promising building material owing to its ability to form predictable secondary structures through sequence-directed hybridization. [ 1 , 2 ] It has been shown that DNA can be precisely designed with specifi c sequences and self-assemble into two-or three-dimensional nanostructures, [3][4][5][6][7][8][9] fabricated to nanomachines or motors, [10][11][12][13] or used as a programmable template to direct the assembly of nanoparticles. [14][15][16][17] Recently, the concept of DNA assembly has been expanded to construct "DNA hydrogels", which are crosslinked networks swollen in an aqueous phase. [18][19][20][21][22][23][24][25][26][27][28][29][30][31] Though hydrogels have great potential in biological and medical applications, [32][33][34][35][36] such as drug and gene delivery, biosensing, and tissue engineering, studying the preparation of DNA hydrogels with designable properties is still in its early stages. In the past, several methods have been reported to prepare DNA hydrogels, for example, DNA directly extracted from the nucleus in nature, behaves like a long linear polymer and forms a hydrogel via physical entanglement or by chemical crosslinking of small molecules. [ 18 − 20] Similarly, DNA can be used as a negatively charged polymer and form a complex with cationic (poly)electrolytes through electrostatic interactions. [ 21 , 22 ] However, both methods treated DNA as a polymer and did not take advantage of the self-assembly of DNA into ordered structures, therefore, the resulting hydrogels lacked precise structural control and specifi c responses. Instead of using physical interactions, DNA can be covalently grafted onto synthetic polymers and serve as a cross-linker, the recognition of complementary DNA strands leads to crosslinking of polymer chains and causes hydrogel formation. [ 23 − 28] In general, the preparation of a DNA-polymer hybrid requires laborious modifi cation steps, and an easy and fast strategy to build tailored DNA hydrogels is desired. Luo and his coworkers have developed a new approach to construct pure DNA hydrogels: using well-designed DNA sequences, selfassembled DNA building blocks with more than two branches could be prepared and further enzymatic ligation between the building blocks led to DNA hydrogel formation. [ 29 ] These DNA hydrogels have been demonstrated for potential applications in controllable drug release [ 29 ] and cell-free protein-producing systems, [ 30 ] however, the enzymatic ligation is rather slow and the preparation is time-consuming. More recently, we have reported that pure DNA hydrogels could be made based on duplex formation and intermolecular i-motif structures. The DNA hydrogels showed a fast sol-gel transition upon changes in the pH, that is, within minutes, and released cargoes in a pH-controlled manner. [ 31 ] However, these DNA hydrogels were not stable under physiological conditions, which limited their in-vivo applications.Herein, we propose a new and general platform to create pure DNA hydrogels t...

Visual optical biosensors based on DNA-functionalized polyacrylamide hydrogels

“…Hydrogels can be made up of pure DNA [41,42]. From the analytical chemistry standpoint however, such gels are very expensive and unlikely to have good sensitivity.…”

Development of DNA Based Active Macro–Materials for Biology and Medicine: A Review

“…reported synthesis of pure DNA hydrogels, based on self-assembled DNA building blocks with more than two branches. These DNA hydrogels showed thermal and enzymatic responsive properties (Xing et al 2011). DNA can also be covalently grafted onto synthetic polymers and serve as a cross-linker .…”

Structural Hierarchy in DNA Hydrogels

“…DNAcross-linked PAA mgel could be used to release nano particles for potential drug-delivery vehicles in response to right stimulus [7]. DNA hydrogels reversibly respond to thermal stimulus, by switching between the gel and sol state (transition temperature) and enzymes when restriction sites are inserted into one of the building blocks [8].…”