Functional DNA Based Hydrogels: Development, Properties and Biological Applications

Abstract

DNA-based nanostructures have emerged as a versatile component for nanoscale construction of soft materials. Multiple structural, functional properties and versatility in conjugation with other biomolecules made DNA the material of choice to use in various biomedical applications. DNA-based hydrogels significantly attracted attention in recent years owing to their properties and applications in biosensing, bioimaging, and therapeutics. Here, we summarize the recent advances in the area of DNA hydrogels where these are used either as structural material or as functional entities to make hybrid constructs with various biomedical applications. Multiple synthetic routes for constructing DNA hydrogels are summarized first, where the structural motifs and spatial arrangements are considered for the classification of DNA materials. We then present the characterization and properties of DNA hydrogels using multiple imaging and biophysical techniques. Further, different biomedical applications of DNA hydrogels are presented such as biosensing, bioimaging, and targeted drug delivery and as scaffolds to program cellular systems. Last, we discuss the vision and potential of DNA based hydrogels as an emerging class of therapeutically important devices for theragnostic and other biological applications.

Stimuli Responsive, Programmable DNA Nanodevices for Biomedical Applications

“…Switchable DNA hydrogels can also be made exclusively from DNA. The simple and easiest way to form DNA hydrogels is by polymerizing branched DNA motifs like a three-way junction or four-way junction, developing through self-assembly of DNA hydrogels ( Nagahara and Matsuda, 1996 ; Li et al, 2016b ; Shahbazi et al, 2018 ; Morya et al, 2020 ) ( Figure 6A ). Different methods are being used to enhance the assembly rate of DNA hydrogel formation, like the use of ligating enzymes ( Figure 6B ) ( Um et al, 2006 ), polymerase chain reaction ( Figure 6C ) ( Hartman et al, 2013 ), rolling circle amplification ( Figure 6D ) ( Lee et al, 2012b ), hybridization chain reaction ( Figure 6E ) ( Wang et al, 2017b ).…”

“… DNA based hydrogels formation by (A) self-assembly of complimentary base pairing ( Xing et al, 2011 ), (B) enzymatic ligation ( Um et al, 2006 ), (C) polymerase chain reaction ( Hartman et al, 2013 ), (D) DNA synthesized in situ via rolling circle amplification (RCA) having a large amount of physical entanglement ( Lee et al, 2012b ), (E) hybridization chain reaction ( Wang et al, 2017b ) and (F) DNA base pairing induced gelation of acrylamide ( Nagahara and Matsuda, 1996 ). Reproduced with permission from ref Morya et al (2020) . Copyright 2020, American Chemical Society (ACS).…”

“…DNA based responsive hydrogels have been explored in many areas, majorly in sensing, capturing, and controlled release ( Xiong et al, 2013 ). Different DNA based hydrogels responsive to various stimuli like pH, ions, biomolecules, enzymes, cDNA have been developed to apply in sensing and biomedical applications ( Morya et al, 2020 ). Sensing of Cu +2 has been demonstrated by using Cu +2 DNAzyme sequence as the cross-linker for polymer matrix.…”

Development, Preparation, and Biomedical Applications of DNA-Based Hydrogels

“…Besides the general characteristics of hydrogels, it also has the advantages of good selection specificity, structural designability, and precise molecular recognition ability. Therefore, DNA-based hydrogels have shown excellent development and clinical application prospects in the fields of drug delivery, biosensing, tissue engineering, protein engineering, and cell imaging ( Gačanin et al, 2020 ; Li et al, 2020 ; Morya et al, 2020 ). With the continuous deepening of the research, by using the characteristics of DNA molecules, introducing other functional molecules or elements into DNA, or combining with other functional materials, researchers have developed various crosslinking methods for the preparation of pure DNA-based hydrogels or DNA-based hybrid hydrogels.…”

Computational studies of a DNA-based aptasensor: toward theory-driven transduction improvement.

“…Recent advances in designing functional DNA architectures 7,8 allow to consider a new class of highly sensitive aptasensors that switch their entire conformation even if only few bases are involved in a target binding process. In most of the cases, the aptamer sequence is introduced inside a host matrix (scaffold) participating in its overall 3Dstructure.…”