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DNA-based nanocomposite hydrogel as a potent injectable drug delivery platform

(Nanowerk Spotlight) DNA is the carrier of genetic information of all living beings on earth. The nitrogenous base sequences along the DNA chain are responsible for the encoding and transmission of genetic information.
Besides being a genetic material, DNA can also be considered as a chemical entity and hence can be exploited as a base matrix to form tissue engineering scaffolds and drug delivery platforms.
From a chemical perspective, DNA is a long chain polymer consisting of monomeric repeat units. Each repeat unit consists of a deoxyribose sugar molecule linked to a phosphate group. Every monomeric unit is also connected to one of the four nitrogenous bases.
The base pairing interactions between the DNA strands are highly specific. Together with the binding of other substances to the backbone, this can be exploited to construct three-dimensionally interconnected hydrogel networks.
Sayantani Basu, a PhD student from the lab of Professor Arghya Paul (BioIntel Research Group) at the University of Kansas, Lawrence, has been working on the utilization of DNA as a high molecular weight polymeric chain in order to form hydrogel networks for tissue regeneration and drug delivery applications.
They have designed shear thinning hydrogels, which can be passed through a 22-gauge syringe by taking advantage of the native chemical structure of DNA and its specific base pairing interactions.
"As a bio and nano-materials engineering lab we are constantly trying to explore the structural properties of different polymers and nanoparticles to design smart materials for diverse biomedical applications including regenerative medicine," says Dr. Arghya Paul.
Previous studies from Paul's BioIntel Research Group at the University of Kansas have shown the use of two-dimensional nanosilicates to form injectable hydrogels (Acta Biomaterialia, "Stem cell-inspired secretome-rich injectable hydrogel to repair injured cardiac tissue")..
In their recent study (ACS Nano, "Harnessing the Noncovalent Interactions of DNA Backbone with 2D Silicate Nanodisks To Fabricate Injectable Therapeutic Hydrogels"), the group has investigated the potential of DNA to form self-assembled injectable hydrogels via physical crosslinking with silicate nanodisks.
DNA-based physically crosslinked hydrogels
DNA-based physically crosslinked hydrogels. (Reprinted with permission by American Chemical Society) (click on image to enlarge)
The DNA-nanosilicate hydrogel is formed by a combination of non-covalent network points without the need of any toxic chemical crosslinkers. DNA denaturation and rehybridization mechanism as well as attractive electrostatic interactions of nanosilicates with the DNA backbone are utilized to generate an interconnected network via a two-step gelation process.
Basu has also shown a sustained release of a model osteogenic drug dexamethasone from the nanoengineered hydrogels and confirmed the bioactivity of the released drugs under lab and preclinical settings to promote bone regeneration.
The animal work was done in collaboration with Professor Jinxi Wang, who directs the Harrington Laboratory for Molecular Orthopedics at University of Kansas Medical Center.
Future work from the research group will focus on the feasibility of the DNA based hydrogels for other more potent drug (small molecules, nucleic acids, growth factors) delivery, and cell delivery applications.
Provided by the University of Kansas as a Nanowerk exclusive.
 

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