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.
Written by:
Guo J, Ogier JR, Desgranges S, Darcy R, O Driscoll C. Are you the author?
Pharmacodelivery group, School of Pharmacy, University College Cork, Cavanagh Pharmacy Building, College Road, Cork, Ireland.
Reference: Biomaterials. 2012 Nov;33(31):7775-84.
doi: 10.1016/j.biomaterials.2012.07.012
PubMed Abstract
PMID: 22828585
UroToday.com Investigative Urology Section
