Kenny, GD and Villegas-Llerena, C and Tagalakis, AD and Campbell, F and Welser, K and Botta, M and Tabor, AB and Hailes, HC and Lythgoe, MF and Hart, SL (2012) Multifunctional receptor-targeted nanocomplexes for magnetic resonance imaging and transfection of tumours. Biomaterials , 33 (29) 7241 - 7250. 10.1016/j.biomaterials.2012.06.042.
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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.
|Title:||Multifunctional receptor-targeted nanocomplexes for magnetic resonance imaging and transfection of tumours.|
|Keywords:||Animals, Cell Line, Tumor, Contrast Media, Female, Gadolinium, Gene Transfer Techniques, Genetic Therapy, Kinetics, Ligands, Liposomes, Luciferases, Magnetic Resonance Imaging, Mice, Models, Chemical, Nanoparticles, Nanotechnology, Neoplasm Transplantation, Neoplasms, Neurotensin, Peptides, Tetanus Toxin, Transfection|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Metabolism and Experimental Therapeutics|
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health > Department of Infection and Immunity > ICH - Molecular Immunology Unit
UCL > School of BEAMS > Faculty of Maths and Physical Sciences > Chemistry
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