Lipid peptide nanocomplexes for gene delivery and magnetic resonance imaging in the brain

JOURNAL OF CONTROLLED RELEASE

卷:162

Article

Writer, Michele J.¹  Kyrtatos, Panagiotis G.^2,3  Bienemann, Alison S.⁴  Pugh, John A.⁵  Lowe, Andrew S.^2,3  Villegas-Llerena, Claudio¹  Kenny, Gavin D.¹  White, Edward A.⁴  Gill, Steven S.⁴  McLeod, Cameron W.⁵  Lythgoe, Mark F.^2,3  Hart, Stephen L.¹ 

[1] UCL Inst Child Hlth, Mol Immunol Unit, London WC1N 1EH, England

[2] UCL, Ctr Adv Biomed Imaging, Dept Med, London WC1E 6DD, England

[3] UCL, UCL Inst Child Hlth, London WC1E 6DD, England

[4] Univ Bristol, Funct Neurosurg Res Grp, Inst Clin Neurosci, Southmead Hosp, Bristol BS16 1LE, Avon, England

[5] Univ Sheffield, Ctr Analyt Sci, Sheffield S10 2TN, S Yorkshire, England

关键词: Nanoparticle;    Gene delivery;    MRI;    Brain;    Targeting;   

DOI  :  10.1016/j.jconrel.2012.07.002

来源: Elsevier

【 摘 要 】

Gadolinium-labelled nanocomplexes offer prospects for the development of real-time, non-invasive imaging strategies to visualise the location of gene delivery by MRI. In this study, targeted nanoparticle formulations were prepared comprising a cationic liposome (L) containing a Gd-chelated lipid at 10, 15 and 20% by weight of total lipid, a receptor-targeted, DNA-binding peptide (P) and plasmid DNA (D), which electrostatically self-assembled into LPD nanocomplexes. The LPD formulation containing the liposome with 15% Gd-chelated lipid displayed optimal peptide-targeted, transfection efficiency. MRI conspicuity peaked at 4 h after incubation of the nanocomplexes with cells, suggesting enhancement by cellular uptake and trafficking. This was supported by time course confocal microscopy analysis of transfections with fluorescently-labelled LPD nanocomplexes. Gd-LPD nanocomplexes delivered to rat brains by convection-enhanced delivery were visible by MRI at 6 h, 24 h and 48 h after administration. Histological brain sections analysed by laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) confirmed that the MRI signal was associated with the distribution of Gd3+ moieties and differentiated MRI signals due to haemorrhage. The transfected brain cells near the injection site appeared to be mostly microglial. This study shows the potential of Gd-LPD nanocomplexes for simultaneous delivery of contrast agents and genes for real-time monitoring of gene therapy in the brain. (C) 2012 Elsevier B. V. All rights reserved.

【 授权许可】

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