Biomedical Engineering Reference
In-Depth Information
report gene expression of the PAMAM-PEG-RVG29/DNA NPs was observed
in the brain, and significantly higher than unmodified NPs.
Huang et al. developed a PAMAM-based glioma-targeting delivery system
by conjugating a chlorotoxin ligand to PAMAM via bifunctional PEG.
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The
results showed that in vivo distribution and gene expression of this compound
were significantly broader and higher in glioma than with unmodified
PAMAM. In the study of Huang et al., angiopep-2, which can target the
low-density lipoprotein receptor-related protein-1 (LRP1) expressed on
BCECs and glial cells, was exploited as the targeting ligand to conjugate
PAMAM via bifunctional PEG to form a glial cell targeting gene vector.
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The
results showed that in vivo biodistribution of PAMAM-PEG-angiopep/DNA
NPs in the brain, especially in the tumor site, was much more obvious due to
the enhanced permeability and retention (EPR) effect and angiopep-2 targeting
ability. This compound showed low cytotoxicity after in vitro transfection. Ke
et al. synthesized PAMAM-PEG-angiopep for brain-targeting gene delivery
both in vitro and in vivo.
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The cellular uptake of the angiopep-modified NPs
was in competition with angiopep-2, receptor-associated protein, and
lactoferrin, indicating that LRP1-mediated endocytosis may be the main
mechanism of cellular internalization of angiopep-modified NPs. Also the
angiopep-modified NPs showed higher efficiency in BBB than unmodified NPs
in an in vitro BBB model, and accumulated in brain more in vivo.
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4.4.2 Polypropylenimine Dendrimers
As an alternative to PAMAM dendrimers, various polypropylenimine
dendrimer-based compounds have been synthesized and investigated for gene
transfer. Duf`s' group have focused on the synthesis of gene vectors based on
polypropylenimine dendrimers. They demonstrated that the conjugation of
transferrin (TF) to the G3 polypropylenimine dendrimer led to an improved
tumor specificity of gene expression and sustained tumor regression after
intravenous administration without visible secondary effects to the mice.
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Recently, they further found that TF-modified polypropylenimine dendrimer
complexed to a plasmid DNA encoding p73 led to an enhanced anti-proliferative
activity in vitro and in vivo compared to the unmodified dendriplex.
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On the
basis that amino acids such as arginine, lysine, and leucine are involved in
enhancing DNA transportation into cells, the group grafted these amino acids
onto polypropylenimine dendrimers.
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These amino acid-modified dendrimers
showed enhanced anti-proliferative activity in vitro and improved tumor gene
expression in vivo compared to unmodified dendrimer.
Minko's group investigated the ability of superparamagnetic iron oxide
(SPIO) nanoparticles and polypropylenimine G5 dendrimers to cooperatively
provoke siRNA complexation in order to develop a targeted, multifunctional
siRNA delivery system for cancer therapy.
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A PEG coating and a cancer-
specific targeting moiety (LHRH peptide) have been incorporated into SPIO-PPI
G5-siRNA complexes to enhance serum stability and selective internalization by
