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: 12.11). 08/2005; 127(30):10676-85. DOI: 10.1021/ja0516460
Source: PubMed


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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    • "Metallic or metal oxide-based nanosystems offer interesting properties for delivery and selective release of drugs in tumours. Nanosystems containing iron oxide, such as " magnetoliposomes " , can accumulate in particular sites of the body under the influence of an external magnetic field and can also act as contrast agents for magnetic resonance imaging [113] [114]. Higher magnetic fields can be used to trigger drug release from the system once it has been concentrated in the tumour. "
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    ABSTRACT: Chemotherapy for AML is hampered by severe side-effects and failure to eliminate all the blasts that eventually leads to relapse. The use of nanosized particulate drug carriers such as liposomes and polymeric nanoparticles has the potential to improve AML therapy by delivering more of the drug to the disease site, thereby reducing toxicity. For example, encapsulation in liposomes reduces the cardiotoxicity of anthracyclines, giving an improved therapeutic index. Moreover, when the surface properties are engineered appropriately, nanocarriers remain in the circulation and extravasate in tissues with sinusoidal capillaries, one of which is bone marrow, leading to a more favourable distribution of the associated drug. Drug carrier technology contributes to the development of newer drugs, such as nucleic acids that can be protected from degradation and delivered into cells, thus opening the way for gene-silencing strategies. Furthermore, carrier systems provide a means of dispersing poorly water-soluble molecule for in vivo administration and thus increase the “druggability” of new lead compounds, such as heat-shock protein inhibitors. Particulate carriers can transport more than one active agent, allowing synergistic action and theranostic strategies. Notably, phase I and II clinical trials are being performed with CPX-351, a liposomal formulation containing cytarabine and daunorubicin at an optimal ratio. Finally, by attaching suitable ligands to the nanocarrier surface, specific targeting to AML cells can be achieved. In this review, we give examples of successful targeting to folate and transferrin receptors against AML.
    Current Pharmaceutical Biotechnology 08/2015; 16(11). DOI:10.2174/1389201016666150817095045 · 2.51 Impact Factor
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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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    • "Liposomes and magnetic liposomes exhibited a good proliferation probably due to the biocompatibility of the liposome system with the cell compartment. Previous study revealed that the encapsulation of surface-modified magnetic nanoparticles into the liposome compartment totally resolved the problems related to the physical behavior of charged surface nanoparticles which tend to react with the serum proteins which might be present on the cell culture medium [40]. Eventually, these results confirmed that drug carriers exhibited no cytotoxicity against L-929 cells, suggesting good biocompatibility. "
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    ABSTRACT: In this study, we developed the cancer treatment through the combination of chemotherapy and thermotherapy using doxorubicin-loaded magnetic liposomes. The citric acid-coated magnetic nanoparticles (CAMNP, ca. 10 nm) and doxorubicin were encapsulated into the liposome (HSPC/DSPE/cholesterol = 12.5:1:8.25) by rotary evaporation and ultrasonication process. The resultant magnetic liposomes (ca. 90 to 130 nm) were subject to characterization including transmission electron microscopy (TEM), dynamic light scattering (DLS), X-ray diffraction (XRD), zeta potential, Fourier transform infrared (FTIR) spectrophotometer, and fluorescence microscope. In vitro cytotoxicity of the drug carrier platform was investigated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using L-929 cells, as the mammalian cell model. In vitro cytotoxicity and hyperthermia (inductive heating) studies were evaluated against colorectal cancer (CT-26 cells) with high-frequency magnetic field (HFMF) exposure. MTT assay revealed that these drug carriers exhibited no cytotoxicity against L-929 cells, suggesting excellent biocompatibility. When the magnetic liposomes with 1 μM doxorubicin was used to treat CT-26 cells in combination with HFMF exposure, approximately 56% cells were killed and found to be more effective than either hyperthermia or chemotherapy treatment individually. Therefore, these results show that the synergistic effects between chemotherapy (drug-controlled release) and hyperthermia increase the capability to kill cancer cells.
    Nanoscale Research Letters 09/2014; 9(1):497. DOI:10.1186/1556-276X-9-497 · 2.78 Impact Factor
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