Biomedical Engineering Reference
In-Depth Information
changes in the optical length for biosensing applications. Extracted from (Tierney & Stokke
2009). (
B
) DNA-only hydrogels based on branched Y-shaped DNA unit. Black i motif with
cytosine-rich regions crosslinks adjacent Y units (B1). The DNA gel prepared from this
design exhibited responsiveness to pH, in low pH where gold naoparticle (AuNP) was
trapped in the gel (a) and at high pH gel dissociation leading to AuNP release (b) Extracted
from (Cheng et al. 2009). (
C
) Neurite outgrowth on a DNA crosslinked hydrogel. Overlay of
higher power images of MAP2 and Tau-1 stain reveals that axons and dendrites could reside
closely in parallel with each other (C1).
Red: Tau-1
immunostaining;
Green: MAP2
immunostaining;
Blue: GFAP
immunostaining;
Purple: DAPI
staining. Scale bar is 50 m.
Comparison of neurite outgrowth, including mean primary dendrite length, primary
dendrite number, and axonal length per neuron, on DNA gels of two designs. Extracted
from (Jiang et al. 2008b). All images with publisher's permission.
designing responsive DNA gels. Among all the cues is pH due to the fact that certain cancer
types are associated with local acidity (Gerweck & Seetharaman 1996). DNA motifs sensitive
to changes in H+ concentration has been incorporated in the DNA based hydrogel to realize
pH responsiveness. A DNA hydrogel in which gel-'drug' interactions are pH dependent
was also proposed (Tang et al. 2009) (
Figure 6B
) along with others gels (Roberts et al. 2007)
(
Table 2
). In this design, the electrostatic interactions that retain drugs in the gel network
can be reduced resulting in subsequent drug release (Tang et al. 2009). Besides pH,
temperature may be another environmental trigger for drug release, particularly for those
diseases with local temperature change (e.g., (Hildebrandt-Eriksen et al. 2002, Letchworth &
Carmichael 1984)). Thermal responsiveness of the DNA hydrogel has been designed based
on the temperature-dependent hybridization, sol-gel transition or physical properties (Costa
et al. 2007, Lin et al. 2004b, Topuz & Okay 2008). Ion strength or concentration has also been
explored to initiate drug release using DNA based macromaterials (Costa et al. 2006.,
Horkay & Basser 2004).
These hydrogels responsive to environmental factors hold promises in facilitating targeted
delivery of therapeutic reagents, while their application has inherent limitation. First, their
application is limited to where such environmental alterations exist; and second, their
controllability is limited due to undesired environmental changes that may occur; third,
their applicability is limited when temporal control in delivery is desired. Looking to
expand the scope of application, some investigators attempted to develop dynamic DNA gel
system without the need of environmental factors. DNA strand per se is naturally an ideal
candidate. Lin and colleagues demonstrated possibility of triggering de-gelation by
delivering ssDNA (Lin et al. 2006), and a similar scheme was adopted by Wei et al.. in
designing a DNA gel capable of releasing proteins based on aptamer-thrombin interactions
(Wei et al. 2008). Aiming at the same application relying on DNA aptamer-protein
interactions, a latest study explored a hydrogel system capable of sustained protein release
(Soontornworajit et al.). Diffusion profile and relationship between cargo size and pore size
of this system were studied, and it was found that the nano-scale particles can be trapped
even their size is smaller than the average pore size of the hydrogel network (Liedl et al.
2007). In addition to DNA strands, by using the similar system, adenosine has also been
shown as the trigger for changes based on its interactions with aptamers (Yang et al. 2008).
A recent work reported the enzyme triggered release of DNA in a polymer network with
grafted DNA duplex (Venkatesh et al. 2009). This system is based on the conventional
crosslinking but contains Acrydite modified DNA recognized by specific enzymes.
