Magnetoliposomes as Multimodal Contrast Agents for Molecular Imaging and Cancer Nanotheragnostics

Fattahi, Hassan; Laurent, Sophie; Liu, Fujun; Arsalani, Nasser; Elst, Luce Vander; Müller, Robert N.

doi:10.2217/nnm.11.14

Cited by 86 publications

(56 citation statements)

References 87 publications

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“…SPIOs are the most popular contrast agents for tracking and studying stem cells by MRI in various fields such as cancer diagnosis and therapy [25,26], clinical studies and therapy [27,28], and stem cell-based transplantation ther-apy [29][30][31]. However, general SIPOs require the addition of a transfection agent, such as Poly-L-lysine (PLL), for efficient cellular uptake [32].…”

Section: Discussionmentioning

confidence: 99%

Labeling of cynomolgus monkey bone marrow-derived mesenchymal stem cells for cell tracking by multimodality imaging

Ren

Wang

Zou

et al. 2011

Sci. China Life Sci.

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Recently, transplantation of allogeneic and autologous cells has been used for regenerative medicine. A critical issue is monitoring migration and homing of transplanted cells, as well as engraftment efficiency and functional capability in vivo. Monitoring of superparamagnetic iron oxide (SPIO) particles by magnetic resonance imaging (MRI) has been used in animal models and clinical settings to track labeled cells. A major limitation of MRI is that the signals do not show biological characteristics of transplanted cells in vivo. Bone marrow mesenchymal stem cells (MSCs) have been extensively investigated for their various therapeutic properties, and exhibit the potential to differentiate into cells of diverse lineages. In this study, cynomolgus monkey MSCs (cMSCs) were labeled with Molday ION Rhodamine-B™ (MIRB), a new SPIO agent, to investigate and characterize the biophysical and MRI properties of labeled cMSCs in vitro and in vivo. The results indicate that MIRB is biocompatible and useful for cMSCs labeling and cell tracking by multimodality imaging. Our method is helpful for detection of transplanted stem cells in vivo, which is required for understanding mechanisms of cell therapy.

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Section: Discussionmentioning

confidence: 99%

Labeling of cynomolgus monkey bone marrow-derived mesenchymal stem cells for cell tracking by multimodality imaging

Ren

Wang

Zou

et al. 2011

Sci. China Life Sci.

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“…102 The encapsulation of the iron cores in PEGylated liposomes affords, as indicated for paramagnetic liposomes, biological stability that improves the contrast agents. Moreover, unlike in the case of SPIONs, liposomes may have some advantages, especially in the field 103 An additional advantage of MLPs over liposomes or over naked iron oxide nanoparticles is that they can be successfully targeted to body parts of interest, to tumors, for example, and their progression in the body can be followed by MRI. Such targeting can be achieved in two ways: 1) by attaching antibodies or ligands to the vesicle surface that can be selectively recognized by specific receptors present in the cells (biological targeting); 104 2) by applying an external magnet near specific body regions where MLPs can then be accumulated (magnetic targeting).…”

Section: Paramagnetic/superparamagnetic Liposomes: Versatile Mri Probesmentioning

confidence: 99%

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

Estelrich¹,

Sánchez-Martín²,

Busquets³

2015

IJN

256

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Magnetic resonance imaging (MRI) has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times ( T 1 , spin–lattice relaxation and T 2 , spin–spin relaxation) of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents) are administered prior to the scanning. Shortening T 1 and T 2 increases the corresponding relaxation rates, 1/ T 1 and 1/ T 2 , producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T 2 -weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions), providing positive contrast in T 1 -weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor) targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of nanoparticles at the site of interest and the bioavailability, respectively. Here, we review the most important characteristics of the nanoparticles or complexes used as MRI contrast agents.

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“…Unlike other methods commonly used in other studies, the new method eliminated the demand for magnetofluid preparation, while the magnetic cores were formed in situ within the liposomes. The theoretical basis for this novel method is that different substances have different abilities to diffuse through the phospholipids bilayer, with small molecules, such as NH 3 2+ were hydrolyzed and precipitated as iron oxides in an alkaline environment. The schematic diagram of the in situ precipitation is shown in Figure 10.…”

Section: Discussionmentioning

confidence: 99%

“…Non-encapsulated FeCl 3 /FeCl 2 was removed by dialysis. In Step 2, the liposomes were alkalized by adding NH 3 to raise the pH to a critical value and incubated at a certain temperature for a certain time. After centrifugation and dialysis, the purified magnetoliposomes were obtained.…”

Section: Introductionmentioning

confidence: 99%

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In situ precipitation: a novel approach for preparation of iron-oxide magnetoliposomes

Xia

Chen

Armah³

et al. 2014

IJN

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Background Conventional methods of preparing magnetoliposomes are complicated and inefficient. A novel approach for magnetoliposomes preparation was investigated in the study reported here. Methods FeCl 3 /FeCl 2 solutions were hydrated with lipid films to obtain liposome-encapsulated iron ions by ultrasonic dispersion. Non-encapsulated iron ions were removed by dialysis. NH 3 · H 2 O was added to the system to adjust the pH to a critical value. Four different systems were prepared. Each was incubated at a different temperature for a different length of time to facilitate the permeation of NH 3 · H 2 O into the inner phase of the liposomes and the in situ formation of magnetic iron-oxide cores in the liposomes. Single-factor analysis and orthogonal-design experiments were applied to determinate the effects of alkalization pH, temperature, duration, and initial Fe concentration on encapsulation efficiency and drug loading. Results The magnetoliposomes prepared by in situ precipitation had an average particle size of 168±14 nm, zeta potential of −26.2±1.9 mV and polydispersity index of 0.23±0.06. The iron-oxide cores were confirmed as Fe 3 O 4 by X-ray diffraction and demonstrated a superparamagnetic response. Encapsulation efficiency ranged from 3% to 22%, while drug loading ranged from 0.2 to 1.58 mol Fe/mol lipid. The optimal conditions for in situ precipitation were found to be an alkalization pH of 12, temperature of 60°C, time of 60 minutes, and initial Fe concentration of 100 mM Fe 3+ + 50 mM Fe 2+ . Conclusion In situ precipitation could be a simple and efficient approach for the preparation of iron-oxide magnetoliposomes.

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Magnetoliposomes as Multimodal Contrast Agents for Molecular Imaging and Cancer Nanotheragnostics

Cited by 86 publications

References 87 publications

Labeling of cynomolgus monkey bone marrow-derived mesenchymal stem cells for cell tracking by multimodality imaging

Labeling of cynomolgus monkey bone marrow-derived mesenchymal stem cells for cell tracking by multimodality imaging

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

In situ precipitation: a novel approach for preparation of iron-oxide magnetoliposomes

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