title: Novel multifunctional nanoparticle mediates siRNA tumour delivery, visualisation and therapeutic tumour reduction in vivo.
abstract: RNA interference (RNAi) is being widely explored as a means of tumour therapy due to the specific and potent silencing of targeted genes. However, in vivo delivery of RNAi effectors, such as small interfering RNA (siRNA) and detection of delivery is fraught with problems. Here, we describe novel theranostic PEGylated siRNA nanoparticles termed liposome-entrapped siRNA (LEsiRNA) nanoparticles. Our LEsiRNA nanoparticles are MR sensitive, contain labels for fluorescence microscopy/histology and promote functional siRNA delivery to tumours in mice leading to a significant reduction in both Survivin expression and tumour growth. LEsiRNA nanoparticles, administered by intravenous injection, were shown to accumulate in xenograft tumours by MR contrast image enhancements 24h post-administration. Fluorescence microscopy was used to corroborate the MR results and simultaneously demonstrate co-localisation of nanoparticles and siRNA within the tumours. The LEsiRNA nanoparticle-mediated delivery of the anti-cancer Survivin siRNA causes significant reduction in tumour growth when compared to controls. Our results suggest that LEsiRNA nanoparticles can be valuable as an in vivo delivery agent for siRNA therapy to tumours.
authors.affiliation: Metabolic and Molecular Imaging Group, Imaging Sciences Department, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital, London, UK. g.kenny@ucl.ac.uk
authors.forename: Gavin D
authors.initials: GD
authors.lastname: Kenny
authors.forename: Nazila
authors.initials: N
authors.lastname: Kamaly
authors.forename: Tammy L
authors.initials: TL
authors.lastname: Kalber
authors.forename: Leigh P
authors.initials: LP
authors.lastname: Brody
authors.forename: Meliz
authors.initials: M
authors.lastname: Sahuri
authors.forename: Elham
authors.initials: E
authors.lastname: Shamsaei
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Miller
authors.forename: Jimmy D
authors.initials: JD
authors.lastname: Bell
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002626:Chemistry, Pharmaceutical; D003287:Contrast Media / Q000008:administration & dosage; D004355:Drug Stability; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D008081:Liposomes; D008279:Magnetic Resonance Imaging; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry*; D009369:Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D012097:Repressor Proteins / Q000235:genetics*; D000077022:Survivin
chemical_list: C117749:Birc5 protein, mouse; D003287:Contrast Media; D005456:Fluorescent Dyes; D051034:Inhibitor of Apoptosis Proteins; D008081:Liposomes; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000077022:Survivin