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

Abstract

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.

Continuous intraputamenal convection-enhanced delivery in adult rhesus macaques

“…This study used MRI to follow the distribution of the MR contrast agent, Gd-DTPA. The range of tracers used in CED studies is wide, including small-molecular-weight compounds such as Gd-DTPA, 18,19,32 dendrimers, 21 iron oxides, 20,36 nanoparticles, 33 and viruses 5,32,33 with attached Gd moieties. The Gd-DTPA tracer is a small-molecularweight contrast agent with the widest FDA approval for use in CNS, body, and head and neck applications in both adults and children.…”

Accuracy of direct magnetic resonance imaging-guided placement of drug infusion cannulae

“…2,6,7,18 This delivery method utilizes fluid convection, which is bulk flow of infusate from a single point source (infusion cannula tip) into the surrounding extracellular spaces, driven by a small hydrostatic pressure gradient. 17 Consequently, accurate placement of infusion cannulae is critical to precisely place the infusion point source in a location that ensures optimum distribution of the infusate.…”

Lipid Nanoparticles for Gene Delivery

“…Kenny et al developed an MRI-visible gene delivery nanocomplex system comprised of self-assembling mixtures of liposomes, plasmid DNA, and targeting ligands, which specifically enhanced transfection efficiency and allowed real-time in vivo monitoring of the specific tumor tissue (Kenny et al, 2012). In another study, Writer et al prepared lipid peptide nanocomplexes with Gadolinium-chelated lipid, DNA-binding peptide, and plasmid DNA (Writer et al, 2012). These lipid nanocomplexes can be used for gene delivery and MRI imaging in the brain.…”