Enhanced siRNA Delivery Using a Combination of an
Arginine-Grafted Bioreducible Polymer, Ultrasound, and Microbubbles
in Cancer Cells
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Abstract
RNAi-based
gene therapy for cancer treatment has not shown significant
clinical impact due to poor siRNA delivery to the target site. Here,
we design a nonviral siRNA gene carrier using a combination of an
arginine-grafted bioreducible polymer (ABP), microbubbles (MB), and
ultrasound (US), for targeting vascular endothelial growth factor
(VEGF) in a human ovarian cancer cell line. Newly designed MBs with
a perfluorocrownether gas core show higher stability compared to controls.
Further, MBs in combination with polyplexes show a significant higher
loading capacity compared to naked siRNA. Lastly, only siRNA-ABP-MB
(SAM) complexes in combination with US show significant VEGF knock
down in A2780 human ovarian cancer cell line compared to naked siRNA
when incubated for a short time after sonication treatment