Biomedical Engineering Reference
In-Depth Information
a cocktail of anti-tumour siRNAs targeting VEGF, MDM2, or c-myc
[15]. Furthermore, by coupling protamine with antibodies, targeted
delivery of siRNA to specific cell types
has been shown.
Pirollo and colleagues developed nanoimmunoliposome complexes
that consisted of a siRNA encapsulated by a cationic liposome that
was targeted to primary and metastatic tumours through the surface
addition of an anti-TfR single-chain antibody fragment [16].
In the majority of peptide-based delivery systems, non-covalent
binding of siRNA and protection from serum nucleases are achieved
by simply mixing the siRNA and reagents. This simplicity of peptide-
based methods is a great advantage for systemic delivery when
compared to other delivery techniques.
in vivo
9.2.3
Polymer-Based Delivery Vectors
An additional method for systemic siRNA delivery is through polymer-
based delivery systems. Polymers such as polyethyleneimine (PEI),
chitosan, and poly DL-lactide-co-glycolide (PLGA) serve as efficient
transfection reagents due to their ability to bind and condense
nucleic acids into stabilized nanoparticles.
PEI is probably the most well-studied polymer delivery system
for nucleic acid delivery at local sites as well as systemically. PEI
is a synthetic polymer that can form branched or linear forms of
different lengths [17] that can be conjugated to siRNA alone or
with additional modifications such as PEG or targeting moieties.
PEI-conjugated siRNAs have been used to suppress influenza
virus infection in mice [18] and knockdown the pain receptor for
N-methyl-D-aspartate in rats [19]. Additional conjugations of siRNA
PEI nanoparticles with ligands for molecules highly expressed on
cancer cells have been achieved for systemic administration. siRNAs
targeting survivan, conjugated with PEG and folate were shown to
inhibit the growth of transplanted human epidermal carcinoma cells
in mice [20]. However, PEI has problems with toxicity upon systemic
delivery, although efforts are being made to reduce toxic effects by
modifying its structure [21, 22].
An alternative to PEI is chitosan; a natural polysaccharide that
has many advantages as a siRNA carrier, including low toxicity,
positive charge, and biodegradability [23]. Studies have shown
efficient knockdown of tumournecrosis-factor-alpha (TNF-
α
) ex-
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