Biomedical Engineering Reference
In-Depth Information
for groups injected with the PEI-SA/DOX/siVEGF and PEI-SA/siVEGF
complexes and PEI-SA/DOX nanoparticles were reduced to 13.0%, 33.7%, and
56.7%, respectively, compared with the untreated group. This result suggests a
significant combined effect of co-delivery of DOX and VEGF siRNA by PEI-
SA nanoparticles.
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Cao et al. developed a multifunctional targeting co-delivery system based on
PEG, PCL, and linear PEI. Diblock copolymers of PEI-PCL were synthesized
and assembled into biodegradable nanocarriers for the combined delivery of
BCL-2 siRNA and DOX. The self-assembled micelles could completely inhibit
siRNA migration at an N/P ratio around 5, with the highest loading content of
DOX around 14.6%. Folic acid as a tumor-targeting ligand was conjugated to
a polyanion, poly(ethylene glycol)-block-poly(glutamic acid) (FA-PEG-PGA).
Driven by electrostatic interactions, FA-PEG-PGA was coated onto the
surface of the cationic PEI-PCL nanoparticles pre-loaded with siRNA and
DOX, potentiating ligand-directed delivery to human hepatic cancer Bel-7402
cells. The folate-targeted delivery of BCL-2 siRNA resulted in more significant
gene suppression, inducing cancer cell apoptosis and improved the therapeutic
efficacy of the co-administered DOX. Targeted DOX-loaded micelles
complexed with BCL-2 siRNA incubation in the highest level of apoptosis
(84.2 ¡ 5.4%), which was significantly higher than either targeted blank
micelles complexed with BCL-2 siRNA (23.4 ¡ 2.5%) or targeted DOX-
loaded micelles complexed with scrambled siRNA (42.8 ¡ 4.2%).
Simultaneously delivering siRNA and the drug into the same cancer cells
could yield a synergistic effect of RNA interference and chemotherapy in
cancer.
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The co-delivery polymeric micellar system was also utilized to overcome
multidrug resistance. Xiong et al. modified PEO-b-PCL block copolymers with
functional groups on both blocks. The functional group on the PCL block was
used to incorporate short polyamines for complexation with siRNA or to
chemically conjugate DOX via a pH-sensitive hydrazone linkage. The PEO
shell was conferred by attaching two ligands, i.e. the integrin a
v
b
3
-specific
ligand (RGD4C) for active cancer targeting and the cell-penetrating peptide
TAT for membrane activity. This system was used to improve the efficacy of
DOX in multidrug-resistant MDA-MB-435 human tumor models that
overexpress P-glycoprotein (P-gp), by simultaneous intracellular delivery of
DOX and siRNA against P-gp expression. RGD/TAT-micelles with DOX and
MDR-1 siRNA demonstrated a maximum of y70% of cell growth inhibition.
Dy677-labeled siRNA was also used to assess the in vivo stability of the siRNA
carrier. Significant Dy677-siRNA fluorescence was observed in tumors 24 h
after injection, suggesting that these micelles could stably complex and protect
siRNA in the micelle core and deliver the siRNA into tumor tissue, while
NON-micelles/Dy677-siRNA did not show obvious fluorescence accumulation
in the tumor, which indicated this multifunctional polymeric micellar system
could target a
v
b
3
-positive tumors in vivo.
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