TY  - JOUR
AV  - public
SN  - 0142-9612
TI  - Multifunctional receptor-targeted nanocomplexes for magnetic resonance imaging and transfection of tumours.
EP  -  7250
IS  - 29
N1  - 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.
KW  - Animals
KW  -  Cell Line
KW  -  Tumor
KW  -  Contrast Media
KW  -  Female
KW  -  Gadolinium
KW  -  Gene Transfer Techniques
KW  -  Genetic Therapy
KW  -  Kinetics
KW  -  Ligands
KW  -  Liposomes
KW  -  Luciferases
KW  -  Magnetic Resonance Imaging
KW  -  Mice
KW  -  Models
KW  -  Chemical
KW  -  Nanoparticles
KW  -  Nanotechnology
KW  -  Neoplasm Transplantation
KW  -  Neoplasms
KW  -  Neurotensin
KW  -  Peptides
KW  -  Tetanus Toxin
KW  -  Transfection
Y1  - 2012/10//
UR  - http://dx.doi.org/10.1016/j.biomaterials.2012.06.042
ID  - discovery1360272
N2  - 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.
SP  - 7241 
VL  - 33
A1  - Kenny, GD
A1  - Villegas-Llerena, C
A1  - Tagalakis, AD
A1  - Campbell, F
A1  - Welser, K
A1  - Botta, M
A1  - Tabor, AB
A1  - Hailes, HC
A1  - Lythgoe, MF
A1  - Hart, SL
JF  - Biomaterials
ER  -