Efficient Delivery of Small Interfering RNAs Targeting Particular MRNAs into Pancreatic Cancer Cells Inhibits Invasiveness and Metastasis of Pancreatic Tumors

Overview

Journal Oncotarget

Specialty Oncology

Date 2019 May 14

PMID 31080558

Citations 11

Authors

Keisuke Taniuchi

Toshio Yawata

Makiko Tsuboi

Tetsuya Ueba

Toshiji Saibara

Affiliations

Soon will be listed here.

Abstract

We report the use of small interfering RNAs (siRNAs) against , , , , , and and folic acid (FA)-modified polyethylene glycol (PEG)-chitosan oligosaccharide lactate (COL) nanoparticles for targeting, imaging, delivery, gene silencing, and inhibition of invasiveness and metastasis in an orthotopic xenograft model. assays revealed that these siRNA-FA-PEG-COL nanoparticles were specifically inserted into pancreatic cancer cells compared to immortalized normal pancreatic epithelial cells and knocked down expression of the corresponding targets in pancreatic cancer cells. Cell motility and invasion were significantly inhibited by adding target siRNA-FA-PEG-COL nanoparticles into the culture medium. mouse experiments confirmed that when intravenously delivered, these siRNA-FA-PEG-COL nanoparticles became incorporated into human pancreatic cancer cells in mouse pancreatic tumors. Little accumulation was seen in the normal pancreas and vital organs. All target siRNA-FA-PEG-COL nanoparticles significantly inhibited retroperitoneal invasion. The siRNA-FA-PEG-COL nanoparticles against , , and , which strongly inhibited retroperitoneal invasion and significantly inhibited peritoneal dissemination compared to the other nanoparticles, improved prognosis of the mice. Our results imply that siRNA-FA-PEG-COL nanoparticles against these six targets could have great potential as biodegradable drug carriers. In particular, siRNA nanoparticles against , , and may hold significant clinical promise.

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