Biomedical Engineering Reference
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cancers, tumor biopsies revealed intracellular and dose dependent
localization of the nanoparticles. In addition, specific reductions
of both RRM2 mRNA and protein levels were observed. 5-RLM-
RACE analyses have shown that this reduction was mediated by
an RNAi mechanism [125]. The paper describing results from the
clinical studies did not contain data regarding the eff ects on human
metabolism and immune response. However, following long-term
administration to mice, no abnormalities in interleukin-12 and IFN-
alpha, liver and kidney function tests, complete blood counts, or
pathology of major organs were observed [42]. The administered
nanoparticles used for delivery of EWS-FLI1 siRNA, demonstrated a
significant and ligand specific inhibition of tumor growth in a murine
model of metastatic Ewing's sarcoma [42].
Figure 5.3 Self-assembly of cyclodextrin-based nanoparticle. The delivery
components are a water-soluble, linear cyclodextrin-containing polymer
(CDP), siRNA, an adamantane (AD)-PEG conjugate (AD-PEG), and the
targeting component that is an adamantane conjugate of PEG that has a
ligand conjugated at the end opposite to the adamantane (AD-PEG-Ligand).
Modified from ref. 122. See also Color Insert.
5.4.6 Arabinogalactan-BasedNanoparticles
Arabinogalactan has been used as a carrier for drug conjugates
[44,126]. Recently, Arabinogalactan-folic acid-drug conjugates for
targeted delivery and activated drug release were prepared [127].
The targeted nanovehicle was formed by conjugation of folic acid
and the anticancer drug methotrexate to arabinogalactan. The use
 
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