Generation of superparamagnetic liposomes revealed as highly efficient MRI contrast agents for in vivo imaging

Laboratoire de Physico-Chimie des Systèmes Polyphasés, UMR CNRS 8612, Université Paris-Sud, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, F-92296 Châtenay-Malabry Cedex, France.
Journal of the American Chemical Society (Impact Factor: 11.44). 08/2005; 127(30):10676-85. DOI: 10.1021/ja0516460
Source: PubMed

ABSTRACT Maghemite (gamma-Fe2O3) nanocrystals stable at neutral pH and in isotonic aqueous media were synthesized and encapsulated within large unilamellar vesicles of egg phosphatidylcholine (EPC) and distearoyl-SN-glycero-3-phosphoethanolamine-N-[methoxy(poly(ethylene glycol))-2000] (DSPE-PEG(2000), 5 mol %), formed by film hydration coupled with sequential extrusion. The nonentrapped particles were removed by flash gel exclusion chromatography. The magnetic-fluid-loaded liposomes (MFLs) were homogeneous in size (195 +/- 33 hydrodynamic diameters from quasi-elastic light scattering). Iron loading was varied from 35 up to 167 Fe(III)/lipid mol %. Physical and superparamagnetic characteristics of the iron oxide particles were preserved after liposome encapsulation as shown by cryogenic transmission electron microscopy and magnetization curve recording. In biological media, MFLs were highly stable and avoided ferrofluid flocculation while being nontoxic toward the J774 macrophage cell line. Moreover, steric stabilization ensured by PEG-surface-grafting significantly reduced liposome association with the macrophages. The ratios of the transversal (r2) and longitudinal (r1) magnetic resonance (MR) relaxivities of water protons in MFL dispersions (6 < r2/r1 < 18) ranked them among the best T2 contrast agents, the higher iron loading the better the T2 contrast enhancement. Magnetophoresis demonstrated the possible guidance of MFLs by applying a magnetic field gradient. Mouse MR imaging assessed MFLs efficiency as contrast agents in vivo: MR angiography performed 24 h after intravenous injection of the contrast agent provided the first direct evidence of the stealthiness of PEG-ylated magnetic-fluid-loaded liposomes.

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    • "This fact, may widen water relaxation because it increases the proton magnetic moment proximity to the huge magnetic moments of the PEGylated SPION (in the liposome aqueous interior), by combining the two contributions presented above. From the comparison of the r 2 values for these PEGylated magnetoliposomes with published values for other magnetoliposomes [26] [27] it can be stated that the PEGylated magnetoliposomes developed in this work can act as a good negative CA (strong effect on reducing T 2 ) for MRI, leading to a possible reduced dose administration to patient. "
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    ABSTRACT: Magnetic core coatings modify the efficiency of nanoparticles used as contrast agents for MRI. In studies of these phenomena, care should be given to take into account possible effects of the specific micro-environment where coated nanoparticles are embedded. In the present work, the longitudinal and transverse relaxivities of superparamagnetic iron oxide nanoparticles stabilized with short-chain polyethylene glycol molecules (PEGylated SPIONs) were measured in a 7T magnetic field. PEGylated SPIONs with two different diameters (5 and 10nm) were studied. Two different PEGylated magnetoliposomes having liposome bilayer membranes composed of egg-phosphatidylcholine, cholesterol and 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine-N-[methoxy PEG-2000] were also studied for their relaxivities, after being loaded with the PEGylated SPION of 5 or 10nm. This type of liposomes is known to have long residence time in bloodstream that leads to an attractive option for therapeutic applications. The influence of the magnetic core coating on the efficiency of the nanosystem as a negative contrast agent for MRI was then compared to the cumulative effect of the coating plus the specific micro-environment components. As a result, it was found that the PEGylated magnetoliposomes present a 4-fold higher efficiency as negative contrast agents for MRI than the PEGylated SPION.
    Materials Science and Engineering C 10/2014; 43C:521-526. DOI:10.1016/j.msec.2014.07.055 · 3.09 Impact Factor
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    • "their significance in identifying microbe-sediment-water interactions, as well as mineral and biogenic origins (Blakemore, 1975; Bazylinski & Frankel, 2004; Dong et al., 2009), and their promising biomedical utilizations (Martina et al., 2005; Sonvico et al., 2005; Dobson, 2006). For example, magnetite (Fe 3 O 4 ) crystals produced by magnetotactic bacteria in vivo commonly exhibit roughly cuboidal or elongated prismaticas well as tooth-, bulletand arrowhead-shaped morphologies, rather than their thermodynamic stable forms (Bazylinski & Frankel, 2003, 2004). "
    Dataset: EMJ-2011-Qu
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    • "As noted in the Introduction, SPIO-loaded PEGylated nano-vesicles have several advantages, including longer circulation in the bloodstream and the potential to carry multiple iron-oxide particles, that enables strong signal enhancement in tumor [21] [22] [23]. It should also be noted that SPIO or USPIO-loaded PEGylated liposomes have been applied for tumor detection and evaluation of tumor treatment with MRI [27] [28] [29] [30]. It is our impression that PEGylated liposomes have characteristics that differ from Nano-PICsomes. "
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    ABSTRACT: Size controllable polyion complex vesicles (PICsomes), composed of biocompatible poly(ethylene glycol) (PEG) and poly(amino acid)s, have an extremely prolonged lifetime in the bloodstream that enables them to accumulate effectively in tumors via the enhanced permeability and retention (EPR) effect. The purpose of this study was to use PICsomes to synthesize a highly sensitive MRI contrast agent for more precise tumor detection. We synthesized SPIO-Cy5-PICsomes (superparamagnetic iron oxide nanoparticle-loaded Cy5-cross-linked Nano-PICsomes) and characterized them using dynamic light scattering and transmission electron microscopy in vitro and evaluated their ability to detect subcutaneously grafted tumors in vivo with MRI. The transverse relaxivity (r2) of the SPIO-Cy5-PICsomes (r2=663±28mM(-1)s(-1)) was 2.54 times higher than that of bare clinically-used SPIO. In in vivo MRI experiments on mice subcutaneously grafted with colon-26 tumor cells, the tumor signal was significantly altered at 3hours after SPIO-Cy5-PICsome administration and persisted for at least 24hours. Small and early-stage in vivo tumors (3days after grafting, approximately 4mm(3)) were also clearly detected with MRI. SPIO-loaded PICsomes are sensitive MRI contrast agents that can act as a powerful nanocarrier to detect small tumors for early diagnosis.
    Journal of Controlled Release 03/2013; 178(3). DOI:10.1016/j.jconrel.2013.03.016 · 7.26 Impact Factor
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