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Anisamide-targeted cyclodextrin nanoparticles for siRNA delivery to prostate tumours in mice

Paper ID Volume ID Publish Year Pages File Format Full-Text
6495 492 2012 10 PDF Available
Title
Anisamide-targeted cyclodextrin nanoparticles for siRNA delivery to prostate tumours in mice
Abstract

A hepta-guanidino-β-cyclodextrin (G-CD), its hepta-PEG conjugate (G-CD-PEG), and the corresponding anisamide-terminated PEG conjugate (G-CD-PEG-AA) have been synthesised and compared as delivery vectors for siRNA to prostate cancer cells and tumours in vivo. The G-CD-PEG-AA.siRNA formulations (in which anisamide targets the sigma receptor), but not the non-targeted formulations, induced prostate cell-specific internalisation of siRNA resulting in approximately 80% knockdown in vitro of the reporter gene, luciferase. Following intravenous administration of the anisamide-targeted formulation in a mouse prostate tumour model significant tumour inactivation with corresponding reductions in the level of vascular endothelial growth factor (VEGF) mRNA were achieved, without demonstrating enhanced toxicity. This data imply significant potential for anisamide-conjugated cyclodextrin vectors for targeted delivery of therapeutic siRNAs in the treatment of prostate cancer.

Keywords
Non-viral vector; PEGylation; Anisamide; Sigma receptor; RNAi; Prostate cancer
First Page Preview
Anisamide-targeted cyclodextrin nanoparticles for siRNA delivery to prostate tumours in mice
Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 31, November 2012, Pages 7775–7784
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering