Anisamide-targeted cyclodextrin nanoparticles for siRNA delivery to prostate tumours in mice
Ogier, Julien R.
O'Driscoll, Caitríona M.
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.
Cyclodextrin , siRNA , Non-viral vector , Pegylation , Anisamide , Sigma receptor , RNAi , Prostate cancer
Guo J., Ogier J., Desgranges S., Darcy R., and O Driscoll CM. (2012) 'Anisamide-targeted cyclodextrin nanoparticles for siRNA delivery to prostate tumours in mice'. Biomaterials, 33 (31):7775-7784. http://dx.doi.org/10.1016/j.biomaterials.2012.07.012
Copyright © 2012, Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Biomaterials. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biomaterials, [33, November 2012] http://dx.doi.org/10.1016/j.biomaterials.2012.07.012