Multifunctional receptor-targeted nanocomplexes for magnetic resonance imaging and transfection of tumours

Gavin D Kenny, Claudio Villegas-Llerena, Aristides D Tagalakis, Frederick Campbell, Katharina Welser, Mauro Botta, Alethea B Tabor, Helen C Hailes, Mark F Lythgoe, Stephen L Hart

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The efficient targeted delivery of nucleic acids in vivo provides some of the greatest challenges to the development of genetic therapies. We aim to develop nanocomplex formulations that achieve targeted transfection of neuroblastoma tumours that can be monitored simultaneously by MRI. Here, we have compared nanocomplexes comprising self-assembling mixtures of liposomes, plasmid DNA and one of three different peptide ligands derived from ApoE, neurotensin and tetanus toxin for targeted transfection in vitro and in vivo. Neurotensin-targeted nanocomplexes produced the highest levels of transfection and showed a 4.7-fold increase in transfected luciferase expression over non-targeted nanocomplexes in Neuro-2A cells. Transfection of subcutaneous Neuro-2A tumours in vivo with neurotensin-targeted nanocomplexes produced a 9.3-fold increase in gene expression over non-targeted controls. Confocal microscopy analysis elucidated the time course of DNA delivery with fluorescently labelled nanocomplex formulations in cells. It was confirmed that addition of a gadolinium lipid conjugate contrast agent allowed real time in vivo monitoring of nanocomplex localisation in tumours by MRI, which was maintained for at least 24 h. The peptide-targeted nanocomplexes developed here allow for the specific enhancement of targeted gene therapy both in vitro and in vivo, whilst allowing real time monitoring of delivery with MRI.

Original languageEnglish
Pages (from-to)7241-50
Number of pages10
JournalBiomaterials
Volume33
Issue number29
DOIs
Publication statusPublished - Oct 2012

Keywords

  • Animals
  • Cell Line, Tumor
  • Contrast Media/pharmacology
  • Female
  • Gadolinium/chemistry
  • Gene Transfer Techniques
  • Genetic Therapy/methods
  • Kinetics
  • Ligands
  • Liposomes/chemistry
  • Luciferases/metabolism
  • Magnetic Resonance Imaging/methods
  • Mice
  • Models, Chemical
  • Nanoparticles/chemistry
  • Nanotechnology/methods
  • Neoplasm Transplantation
  • Neoplasms/pathology
  • Neurotensin/chemistry
  • Peptides/chemistry
  • Tetanus Toxin/chemistry
  • Transfection

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  • Cite this

    Kenny, G. D., Villegas-Llerena, C., Tagalakis, A. D., Campbell, F., Welser, K., Botta, M., Tabor, A. B., Hailes, H. C., Lythgoe, M. F., & Hart, S. L. (2012). Multifunctional receptor-targeted nanocomplexes for magnetic resonance imaging and transfection of tumours. Biomaterials, 33(29), 7241-50. https://doi.org/10.1016/j.biomaterials.2012.06.042