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.
authors: School of Pharmacy, University College Cork, Cork, Ireland.
authors: Jianfeng
authors: J
authors: Guo
authors: Julien R
authors: JR
authors: Ogier
authors: Stephane
authors: S
authors: Desgranges
authors: Raphael
authors: R
authors: Darcy
authors: Caitriona
authors: C
authors: O'Driscoll
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology; D001549:Benzamides / Q000737:chemistry* / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004705:Endocytosis / Q000187:drug effects; D019793:Fluorescein / Q000378:metabolism; D020868:Gene Silencing / Q000187:drug effects; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism; D047392:beta-Cyclodextrins / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D047392:beta-Cyclodextrins; C031215:betadex; D019793:Fluorescein