DNA Nanotechnology and Drug Delivery - DNA Nanotechnology: From Structure to Function - page 312

Fig. 15.1 Overall strategy: ( a ) self-assembled DNA nanotubes (DNA-NTs) contain both Cy3
(a fluorescence dye) and folate (a targeting agent); ( b ) dual-functionalized DNA-NTs specifically
bind to cancer cells through folate-folate receptor ( FR ) interaction (Reprinted with permission
from Ref. [ 4 ]. Copyright 2008 American Chemical Society)

In a control experiment, they put together all the individual DNA strands which
they used for the formation of the functionalized DNA nanotube, but used a quick
cooling protocol so that the strands will not form the correct DNA nanotube
structure. After incubation with the FR-KB cells, they found no clear evidence that
any DNA entered into KB cells, which proved that the DNA nanotube structure is
essential for delivering Cy3 into the KB cells.
Their results also showed that DNA-NTs and cell incubation time and folate
content on the DNA nanotube surface also have certain effects on the cell targeting
and cell uptaking efficacy.
This pioneer research showed that the dual-functionalized DNA-NTs could be
a promising candidate for multifunctional drug delivery nanocarrier. However,
their result brought concerns about the stability of the DNA nanotubes for drug
delivery purpose, since once got into the cells, the structure of their DNA-NTs
were not clearly recognized anymore. One of the possible reasons for the structure
changes might be the relative large size of their DNA nanotubes, 10-40

m, which
might make the nanotubes difficult to maintain their designed structure after the
cell uptaking process. Different designed DNA nanotubes without the palindromic
segments [ 5 ] might provide better control over the length of the DNA nanotubes;
also with the approximately 2 nm cavity of a six-helix bundle DNA nanotube [ 6 ],
it is possible to attach the drug molecules inside the DNA nanotube cavities, which
might help to make controlled-release drug delivery system.

15.3 DNA Tetrahedron as Drug Delivery Nanocarrier

After the work of DNA nanotubes, other DNA 3D structures had since been explored
as potential drug delivery nanocarriers. First, Bermudez's group [ 7 ]testedthe
resistance of DNA tetrahedron structures against enzymatic digestions. The DNA