Biomedical Engineering Reference
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cancer activity was only realized when siRNA therapy was combined
with cisplatin chemotherapy.
92
The partial activity of EGFR siRNA
was related to the anti-apoptosis activity of DOTAP, a component of
the LPD formulation.
92
3.4.1.3.3 Combination treatment: MDM2, c-myc, and
vascular endothelial growth factor
A combination treatment with several different siRNAs might be
synergistic in anti-proliferation of the tumor. Based on the study
by Song
127
enhanced anti-proliferation on the murine B16
melanoma cells has been observed by the simultaneous silencing
of three oncogenes, MDM2, c-myc, and vascular endothelial growth
factor (VEGF). MDM2 is an inactivator of the tumor suppressor p53
gene. c-myc acts as an activated transcription factor, which promotes
cell proliferation. Lastly, VEGF is an angiogenesis factor that is related
to metastasis.
et al.
,
128-130
The combined siRNAs were encapsulated in
the anisamide-targeted LPD formulations. Two consecutive IV
injections at 0.45 mg/kg, a relatively low dose, showed a significant
inhibition effect in lung metastases-bearing mice. Only the siRNAs in
targeted NPs showed an effective synergistic effect of three siRNAs,
which was consistent with the Western blotting analysis data. It
also significantly reduced the number of metastasis nodules in the
lung, while other formulations showed little therapeutic effect. This
suggested that the silencing activity was highly dependent on the
formulation and siRNA sequence. Also, the survival rate of mice
treated with siRNAs in the targeted NPs reached the highest point
(90%) among all the treatment groups on the 23
day. Both the non-
targeted and the targeted NPs significantly improved the survival
of animals compared to that of the free siRNA (
rd
131
At the
therapeutic dose (0.45 mg/kg), the targeted NP did not significantly
elevate the level of any of cytokines, including interleukin-6 (IL-6),
IL-12, tumor necrosis factor, and interferon-α, even after two
consecutive injections. The targeted NP was safe at the therapeutic
dose.
p
< 0.05).
3.4.1.4 Modified LPD formulations
3.4.1.4.1
LPD with guanidinium-containing cationic lipid
Drug resistance in cancer cells is usually caused by the overexpres-
sion of drug efflux transporter proteins, such as P-glycoprotein
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