DNA Nanotechnology and Drug Delivery - DNA Nanotechnology: From Structure to Function - page 318

injection. By measuring bioluminescent intensity in the tumor, their results showed
a decrease of 60% in bioluminescent intensity for both tail-vein and intratumor
injections (Fig. 15.7 ,Ref.[ 12 ]). Their experiments showed that DNA tetrahedron
nanostructures have a promising future as a nanocarrier for in vivo SiRNA and
possible other drugs delivery.
The three wonderful works [ 10 - 12 ] have clearly showed that DNA tetrahedron
nanostructure has the potential to be a universal drug delivery carrier and a
promising future in pharmaceutical field. And DNA tetrahedrons build from three-
point-star motifs [ 13 ], and a single-stranded DNA [ 14 ] might further improve the
stability of the tetrahedrons inside cells. And the reconfigurable operation work of
the DNA tetrahedron [ 15 ] might bring the possibility of controlled release of the
attached drugs.

15.4 DNA Origami Structures as Drug Delivery

Nanocarriers

Meanwhile, DNA origami structures had also been explored as potential drug
delivery nanocarriers. First, Yan's group [ 16 ] tested the stabilities of different
shaped DNA origami nanostructures in lysates from various normal and cancerous
cell lines. After incubating DNA origami nanostructures with cell lysates for up to
12 h, they found the DNA origami structures were still intact and could be separated
from the cell lysates. And even for DNA rectangular origami addressed with
function probes (human -actin gene), their results showed that the DNA origami

structure including the probe were still intact and could be used for RNA detection
after separation from cell lysate. Their results demonstrated that DNA origami
structures could also be used for in vivo bioapplications, including as drug delivery
nanocarriers.
Liedl's group then used a DNA origami nanotube as delivery nanocarrier for
the therapeutic CpG oligodeoxynucleotides [ 17 ]. Their designed hollow tube-
shaped DNA origami structure has a diameter of 20 nm and a length of 80 nm,
assembled from 227 oligonucleotides (staple strands) that fold an 8,634 nucleotide
M13mp18-based single strand. This tube consists of 30 parallel double helices
with maximized surface area for both 62 inner or 62 outer binding sites (handle
sequences H) for cytosine-phosphate-guanine (CpG) plus anchor sequences (CpG-
H's); the handle sequence H is a 18-base long single strand that is complementary
to the anchor sequence H' of the CpG-H's. This CpG-functionalized hollow DNA
origami nanotube once incubated with and uptaken by the cell, they will bind and
activate Toll-like receptor 9 (TLR9) and then the downstream pathway just as Fan's
work [ 8 ] showed (Fig. 15.8 ,Ref.[ 17 ]).
For the cell uptaking test experiment, they incubated the CpG-DNA hollow
origami tubes with freshly isolated spleen cells for up to 3 h. To monitor the
cell uptaking by fluorescence microscopy measurement, they also attached dye

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