Novel multifunctional nanoparticle mediates siRNA tumour delivery, visualisationand therapeutic tumour reduction in vivo

Gavin D. Kenny, Nazila Kamaly, T. L. Kalber, L. P. Brody, Meliz Sahuri, Elham Shamsaei, Andrew D. Miller, Jimmy Bell

Research output: Contribution to journalJournal articleResearchpeer-review

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 24 h 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.
Original languageEnglish
JournalJournal of Controlled Release
Volume149
Issue number2
Pages (from-to)111–116
ISSN0168-3659
Publication statusPublished - 2011
Externally publishedYes

Keywords

  • Liposome
  • Magnetic resonance imaging
  • siRNA
  • Tumour therapy
  • Survivin
  • Paramagnetic

Cite this

Kenny, G. D., Kamaly, N., Kalber, T. L., Brody, L. P., Sahuri, M., Shamsaei, E., Miller, A. D., & Bell, J. (2011). Novel multifunctional nanoparticle mediates siRNA tumour delivery, visualisationand therapeutic tumour reduction in vivo. Journal of Controlled Release, 149(2), 111–116.