Biomedical Engineering Reference
In-Depth Information
Xiong et al. have developed a series of virus-like siRNA carriers, based on
poly(ethylene oxide)-block-poly(e-caprolactone) (PEO-b-PCL) micelles deco-
rated with integrin a
v
b
3
targeting peptide (RGD4C) and/or cell penetrating
peptide (TAT) on the PEO shell, and modified with a polycation (spermine) in
the PCL core for siRNA binding and protection.
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They demonstrated that
RGD and TAT modification increased cellular uptake of siRNA formulated
micelles. These peptide functionalized micelles, especially the RGD/TAT
micelles containing mdr1 siRNA, effectively silenced P-gp expression,
increased DOX intracellular uptake, improved DOX penetration into nuclei,
and finally enhanced DOX cytotoxicity in MDA435/LCC6 DOX-resistant
cells. They further synthesized the degradable PEO-b-PCL block copolymers
for traceable co-delivery of siRNA and DOX, and demonstrated that
incorporation of fluorescent probes in the micellar core allows for in vitro
and in vivo tracking of micelles.
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d
n
4
y
3
n
g
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3
4.7.4 Therapeutic Genes
The efficient delivery of therapeutic genes into cells of interest is a critical
challenge to a broad application of nonviral vectors. In cancer gene therapy,
therapeutic agents including functional normal tumor suppressor genes,
inflammatory immune cytokine genes, and microRNAs are delivered to the
tumor cell using a carrier.
Recently, Dai et al. synthesized a ternary copolymer (PEG-b-PLL-g-lPEI;
PPI) by grafting LMW linear PEI onto PEGylated PLL.
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These compounds
demonstrated higher cell viability and enhanced gene transfer efficiency
compared to PEG-b-PLL. Moreover, remarkable tumor cell apoptosis and
growth inhibition were achieved when the folate-encoded PPI was used to
transfer the TNF-related apoptosis-inducing ligand gene (TRAIL).
Transforming growth factor-b (TGF-b) is a well-known cytokine related to
tissue fibrosis. Recent studies demonstrated that the regulation of TGF-b
levels resulted in a significant therapeutic effect on liver fibrosis. Park et al.
developed a liver-targeted vector for TGF-b siRNA using reducible PEI-
grafted hyaluronic acid (HA) conjugates.
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This system showed low toxicity
and obvious therapeutic effects on liver cirrhosis due to HA receptor-mediated
endocytosis. The TGF-b siRNA/reducible polymer complex showed a feasible
therapeutic effect on liver cirrhosis. This system can be exploited for the target-
specific systemic treatment of various liver diseases.
Arote et al. developed a biodegradable folate conjugated poly(ester amine)
(FP-PEA) vector for dominant-negative c-Jun (TAM67) delivery.
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FP-PEA
showed marked antitumor activity against FR-positive human KB tumors in
nude mice, with no evidence of toxicity after therapy using the TAM67 gene.
Furthermore, the therapeutic effect occurred in the apparent absence of weight
loss or noticeable tumor apoptosis.
