Tumor-homing glycol chitosan/polyethyleneimine nanoparticles for the systemic delivery of siRNA in tumor-bearing mice

Title
Tumor-homing glycol chitosan/polyethyleneimine nanoparticles for the systemic delivery of siRNA in tumor-bearing mice
Authors
허명숙이승영박상진이슬기정현진이소진최용석오유경박재형정서영최귀원김광명권익찬
Keywords
Glycol chitosan; Polyethylenimine; siRNA; Nanoparticle delivery system; Tumor-targeting delivery; Cancer treatment
Issue Date
2010-06
Publisher
Journal of controlled release
Citation
VOL 144, NO 2, 134-143
Abstract
Here, we designed a new nano-sized siRNA carrier system composed of biocompatible/biodegradable glycol chitosan polymer (GC) and strongly positively charged polyethylenimine (PEI) polymers. In order to make a stable and tumor-homing nano-sized carrier, each polymer was modified with hydrophobic 5β-cholanic acid, and they were simply mixed to form self-assembled GC–PEI nanoparticles (GC–PEI NPs), due to the strong hydrophobic interactions of 5β-cholanic acids in the polymers. The freshly prepared GC–PEI NPs showed a stable nanoparticle structure (350 nm) and they presented a strongly positive-charged surface (ζ potential=23.8) that is enough to complex tightly with negatively charged RFP-siRNAs, designed for inhibiting red fluorescent protein (RFP) expression. The siRNA encapsulated nanoparticles (siRNA–GC–PEI NPs) formed more compact and stable nanoparticle structures (250 nm) at 1: 5 weight ratio of siRNA to GC–PEI nanoparticles. In vitro RFP expressing B16F10 tumor cell (RFP/B16F10) culture system, the siRNA– GC–PEI NPs presented a rapid time-dependent cellular uptake profile within 1 h. Moreover, the internalized siRNA–GC–PEI NPs lead to specific mRNA breaks down. Furthermore, our new formulation of siRNA–GC–PEI NPs presented a significant inhibition of RFP gene expression of RFP/B16F10-bearing mice, due to their higher tumor-targeting ability. These results revealed the promising potential of GC–PEI NPs as a stable and effective nano-sized siRNA delivery system for cancer treatment.
URI
http://pubs.kist.re.kr/handle/201004/38159
ISSN
0168-3659
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KIST Publication > Article
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