DNA Nanotechnology and Drug Delivery - DNA Nanotechnology: From Structure to Function - page 317

Fig. 15.7 In vivo pharmacokinetic profile and gene silencing in tumor xenograft mouse model.
( a ) Pharmacokinetic profile of ONPs in KB tumor-bearing mice and ex vivo fluorescence image
of five major organs and tumor 12 h post-injection ( T tumor, Lv liver, S spleen, K kidney,
Lu lung, H heart). A high level of siRNA accumulation occurs in tumor tissue. ( b ) Tumor-
specific accumulation of ONPs as determined by FMT-CT 25 min post-injection ( left CT scan;
right three-dimensional FMT-CT). The highlighted circular region indicates the location of the
tumor xenograft. ( c ) In vivo luciferase silencing in KB tumor xenografts ( n 7; BLI biolumi-

nescence intensity; control, PBS injection; IT intratumoral; IV intravenous; ONPLuc, ONPs with
folate-conjugated anti-luciferase siRNA; siLuc, folate-conjugated anti-luciferase siRNA). siRNA
concentration, 2.5 mg/kg. * P

D

0.002 compared with control. NS not significant.
The four images above the bar graph are live BLI images of mice from each group. Warmer
colors indicate strong BLI in the tumor xenografts. ( d ) Quantitative analysis of luciferase mRNA
expression in KB tumors 2 days after ONP injection ( n D 3; control (PBS injection); ONPLuc
(ONPs with folate-conjugated anti-luciferase siRNA); ONPGFP (ONPs with folate-conjugated
anti-GFP siRNA); Luc). siRNA concentration, 2.5 mg/kg. Luc is a firefly luciferase gene. GAPDH
is used as a housekeeping gene. Luciferase mRNA level is expressed as a ratio with GAPDH
(Luc/GAPDH). * P <

< 0.138, ** P <

0.03 compared with control. NS not significant. ( e ) In vivo live
fluorescence images showing dose-responsive accumulation of ONPs in KB tumors compared with
FA-conjugated siRNA (siRNA alone); animals were treated by systemic injection ( n D

0.05, ** P <

3), and
images are representative of each group (Reprinted by permission from Macmillan Publishers Ltd:
Nature Nanotechnology, Ref. [ 12 ], copyright 2012)

four times longer blood circulation time (t1/2 24.2 min) than the parent siRNA
(t1/2 6 min). This proved that the DNA tetrahedron nanostructure could be used
as a SiRNA nanocarrier for in vivo delivery.
And then they tested the therapeutic potential of DNA tetrahedron nanostructure
as SiRNA nanocarrier. In vivo gene silencing of firefly luciferase expressing
KB xenografts was performed by delivering FA-conjugated DNA tetrahedrons
with anti-luciferase siRNA into mice, either by tail-vein injection or intratumor