Biomedical Engineering Reference
In-Depth Information
cancer cells. Such a modification of siRNA nanoparticles enhanced its
internalization into cancer cells and increased the efficiency of targeted gene
suppression in vitro. Moreover, the developed siRNA delivery system was
capable of sufficiently enhancing in vivo antitumor activity of an anticancer drug
(cisplatin). Recently, they constructed a nanocarrier-based delivery system by
taking advantage of the lessons learned from the problems in the delivery of
DNA.
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In this study, siRNA nanoparticles were first formulated with
polypropylenimine dendrimers. To provide lateral and steric stability to
withstand the aggressive environment in the blood stream, the formed siRNA
nanoparticles were caged with dithiol-containing crosslinker molecules followed
by coating them with PEG. A synthetic analog of a luteinizing hormone-
releasing hormone (LHRH) peptide was conjugated to the distal end of the PEG
polymer to direct the siRNA nanoparticles specifically to the cancer cells. The
results demonstrated that this layer-by-layer modification and targeting
approach conferred the siRNA nanoparticles with stability in plasma and
intracellular bioavailability, and provided for their specific uptake by tumor
cells, accumulation of siRNA in the cytoplasm of cancer cells, and efficient gene
silencing. In addition, in vivo body distribution data confirmed high specificity of
the proposed targeting delivery approach, which created the basis for the
prevention of adverse side effects of the treatment on healthy organs. Hao et al.
modified G3 cationic dendritic polymeric polypropylenimine by pluronic P123
and investigated its use for gene delivery.
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The transfection efficiency of SPC-A1
cells using P123-PPI/DNA nanoparticles was much higher than the transfection
utilizing PPI/DNA nanoparticles. The addition of free P123 during the
preparation of P123-PPI/DNA nanoparticles could significantly enhance the
transfection efficiency in the presence of 10% fetal bovine serum.
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4.4.3 Poly(
L
-lysine) Dendrimers
Peptide dendrimers are constructed by peptide bond linkages from natural or
unnatural amino acids. They share common features with proteins such as
globular structure, water solubility, biocompatibility, and biodegradability.
Poly(
L
-lysine) dendrimers are a new type of polypeptide dendrimer, which have
been explored as gene and drug delivery systems in recent years. Luo et al.
reported the synthesis and characterization of different generations of
dendritic poly(
L
-lysine) vectors and their use for in vitro gene transfection
(Scheme 4.9).
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They found that higher generations tended to produce greater
positive potentials, indicating a stronger potency of the complexes to interact
with negatively charged cell membranes. In vitro and in vivo cytotoxicity results
showed good biocompatibility of the dendrimers. In vitro gene transfection
revealed higher efficiency of G5 than other dendrimers and insensitive
variation to the presence of serum. Al-Jamal et al. reported that G6 PLL
dendrimer has the ability to accumulate and persist in solid tumor sites after
systemic administration and exhibit antiangiogenic activity in the absence of
cytotoxicity.
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