Biomedical Engineering Reference
In-Depth Information
MNPs took on a uniformly spherical morphology with a zeta potential of
around 45 mV and were stabilized by hydrophobic-hydrophobic interactions
in the PCL core, exhibiting a CMC at 2.7 6 10
23
mg mL
-1
. Such MNPs
allowed siRNA loading after nanoparticle formation without a change in
uniformity. The siRNA loaded nanoparticles could be effectively internalized
and subsequently released siRNA in cells, resulting in significant gene
knockdown activity, which was demonstrated by delivering two siRNAs
targeting green fluorescence protein (GFP) that effectively silenced GFP
expression in 40-70% of GFP-expressing HEK293 cells.
62
Anticeramidase
siRNA-loaded nanoparticles (micelleplex
siAC
) showed significant gene knock-
down activities toward the endogenous acid ceramidase (AC) gene in vitro and
a significant inhibition of tumor growth in a BT474 xenograft murine model
via tail vein injection (Figure 7.4). In addition to AC gene silencing,
administration of micelleplex
siAC
in animals inhibited proliferation and
elevated apoptosis in breast tumor cells. An evaluation of immunotoxicity
indicated that this delivery system did not induce an immune response.
70
Qi et al. synthesized siRNA carriers consisting of biodegradable cationic
copolymers of monomethoxy poly(ethylene glycol)-block-poly(e-caprolac-
tone)-block-poly(
L
-lysine) (mPEG-b-PCL-b-PLL, abbreviated as ''M'') with a
PCL block of different lengths. Compared to mPEG-b-PLL (abbreviated as
''P''), M micellar nanoparticles with siRNA had a smaller size. The diameters
of the P-complexes ranged from 130 nm to 300 nm, depending on the N/P
d
n
4
y
3
n
g
|
8
Figure 7.4
(A) Inhibition of BT474 xenograft tumor growth by micelleplex
siAC
. (B)
HE, TUNEL, BrdU, and anticeramidase (AC) analyses of tumor tissues
after treatment for 22 days with various formulations. (C) Examination
of mouse IFN-a, IFN-b, IFN-c, tumor necrosis factor (TNF)-a, and
interleukin (IL)-6 levels in the serum of BT474 xenograft-bearing mice
after 8 or 22 days of intravenous injections of various formulations.
(Adapted from Mao et al.
70
with permission from Elsevier.)
