eprintid: 1360272 rev_number: 54 eprint_status: archive userid: 608 dir: disk0/01/36/02/72 datestamp: 2012-09-11 19:04:54 lastmod: 2021-11-30 22:57:26 status_changed: 2012-09-11 19:04:54 type: article metadata_visibility: show item_issues_count: 0 creators_name: Kenny, GD creators_name: Villegas-Llerena, C creators_name: Tagalakis, AD creators_name: Campbell, F creators_name: Welser, K creators_name: Botta, M creators_name: Tabor, AB creators_name: Hailes, HC creators_name: Lythgoe, MF creators_name: Hart, SL title: Multifunctional receptor-targeted nanocomplexes for magnetic resonance imaging and transfection of tumours. ispublished: pub divisions: UCL divisions: B02 divisions: C10 divisions: D17 divisions: G94 divisions: D13 divisions: G23 divisions: G24 divisions: B04 divisions: C06 divisions: F56 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 note: This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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. date: 2012-10 official_url: http://dx.doi.org/10.1016/j.biomaterials.2012.06.042 vfaculties: VGHCSCI vfaculties: VMPS oa_status: green language: eng primo: open primo_central: open_green article_type_text: Journal Article, Research Support, Non-U.S. Gov't verified: verified_manual elements_source: PubMed elements_id: 437157 doi: 10.1016/j.biomaterials.2012.06.042 pii: S0142-9612(12)00692-8 lyricists_name: Hailes, Helen lyricists_name: Hart, Stephen lyricists_name: Lythgoe, Mark lyricists_name: Tabor, Alethea lyricists_name: Tagalakis, Aristides lyricists_id: HCHAI24 lyricists_id: SLHAR52 lyricists_id: MFLYT72 lyricists_id: ABTAB91 lyricists_id: ATAGA52 full_text_status: public publication: Biomaterials volume: 33 number: 29 pagerange: 7241 - 7250 event_location: UK issn: 0142-9612 citation: Kenny, GD; Villegas-Llerena, C; Tagalakis, AD; Campbell, F; Welser, K; Botta, M; Tabor, AB; ... Hart, SL; + view all <#> Kenny, GD; Villegas-Llerena, C; Tagalakis, AD; Campbell, F; Welser, K; Botta, M; Tabor, AB; Hailes, HC; Lythgoe, MF; Hart, SL; - view fewer <#> (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 <https://doi.org/10.1016/j.biomaterials.2012.06.042>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/1360272/1/1360272.pdf