Biomedical Engineering Reference
In-Depth Information
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Figure 7.10
(A) Schematic illustration of the preparation of disulfide-crosslinked
PIC micelles containing siRNA. (B) Schematic illustration of the
synthesis of PEG-b-PLL derivatives. (C) In vitro gene knockdown of
luciferase in B16F10-luc cells. (D) Behavior of siRNA incorporating
micelles prepared with PEG-b-PLL(X) (X 5 N2IM-IM or MPA)
following intravenous injection. Snapshots of the ear lobe dermis at 1, 3,
and 10 min with Cy5 fluorescence shown as red. (Adapted from Christie
et al.
117
with permission from the American Chemical Society.)
disruption under disulfide-reducing conditions. Blood circulation was most
improved for PEG-b-PLL(N2IM-IM)/siRNA micelles, with a circulation half-
life three-fold longer than naked siRNA.
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7.4 Co-delivery of siRNA and Drugs Based on
Polymeric Micelles
In the past decade, siRNA therapy has achieved in vitro reduction in target
gene expression and promising activity against a wide variety of tumors.
However, because of the multigenic alterations of tumors, the use of siRNAs
as single agents does not seem to be effective in the treatment of malignancies.
Thus, siRNA therapy that interferes with signaling pathways in cell
proliferation and apoptosis are particularly promising in combination with
conventional anticancer treatment. Sp¨ nkuch et al. identified that treatment of
