Molecular Gels for Tissue Engineering - Soft Fibrillar Materials: Fabrication and Applications - page 148

Double-stranded nucleic acids with single-stranded overhangs have demon-
strated gelating potential. Cheng et al . have produced a fast and pH-responsive
gel with three-armed double-stranded deoxyribonucleic acid (DNA) nanostructures
[85]. The gelator, which was termed as the Yunit , is comprised of three 37mer
single stranded DNAs. Of the 37 nucleotides, 11 represent the interlocking motif
domain with 2 cytosine-rich stretches that can be cross-linked to another Y unit.
The remaining 26 nucleotides contain 2 half-complementary sequences that are
essential for the formation of the double-stranded Y shape of the Y unit. Gelation is
evoked by low pH, which encourages the formation of intermolecular interlocking
motif structures. Interlocking domains that were initially separated by electronic
repulsion would be partially protonated upon the addition of hydrochloric acid.
Protonated cytosine residues in the interlocking domain would then formhydrogen
bonds with unprotonated cytosine residues, forming the interlocking motifs that
link different Y units together and form extended interconnected networks.
One important characteristic of this hydrogel is that it is sensitive to pH changes.
To demonstrate this ability, the authors have incorporated water-soluble citrate-
modified 13 nm gold nanoparticles into the hydrogel. The results, as shown in
Figure 4.10, showed that no nanoparticles were released for several days after
the hydrogel was formed. The addition of sodium hydroxide, however, resulted
in rapid release of the entrapped nanoparticles within minutes, suggesting that
the hydrogel is capable of encapsulating small substances with high efficiency
and stability and that the gel can be easily reverted back to its solution state
by changing the environmental pH. In addition, the authors have shown that
the hydrogel stability can be affected by temperature; in particular, the gelling
transition temperature of the DNA hydrogel formed was found to be at 37 ◦ C
at a gelator concentration of 0.6mM. This pH- and temperature-sensitive DNA
hydrogel possesses tremendous potential in the field of controlled release, where
chemicals or biologics can be incorporated in and released from the hydrogel by
responding to local changes in pH and temperature specific to diseased tissues.
While the molecular weights of the DNA gelators used in the above study have
exceeded the limit of 3000 Da, it is worth noting that this hydrogel still shares
many characteristics with classical molecular gels, for example, gelation which is
achieved by self-assembly of individual monomers via non-covalent interactions
and the relative ease of breaking down the gels formed by simply changing the
environmental pH.
In addition to hydrogen bonding as a means of forming DNA hydrogel, it can also
be formed by cross-linking nucleic acids via phosphodiester bonds with DNA ligase.
Such double-stranded DNAs usually possess single-stranded palindromic end
sequences that permit hybridization with complementary sequences. Technically,
this type of DNA hydrogels would not fit the strict definition of molecular gel
because of the high molecular weight of the gelators used and the covalent nature
of the bonds that form the gelation network. However, this type of DNA hydrogels
differs significantly from the other types of chemically cross-linked hydrogels,
for which no potentially harmful chemicals are needed to trigger the gelation
process and the gels formed can be broken down easily with the use of DNA