Toward absolute quantification of iron oxide nanoparticles as well as cell internalized fraction using multiparametric MRI

Iron oxide nanoparticles (IONPs) are widely used as MR contrast agents because of their strong magnetic properties and broad range of applications. The contrast induced by IONPs typically depends on concentration, water accessibility, particle size and heterogeneity of IONP distribution within the microenvironment. Although the latter could be a tool to assess local physiological effects at the molecular level, it renders IONP quantification from relaxation measurements challenging. This study aims to quantify IONP concentration using susceptibility measurements. In addition, further analysis of relaxation data is proposed to extract quantitative information about the IONP spatial distribution. Mesenchymal stem cells were labeled with IONPs and the IONP concentration measured by mass spectroscopy. MR relaxation parameters (T₁, T₂, T₂*) as well as magnetic susceptibility of cylindrical samples containing serial dilutions of mixtures of free and cell‐internalized IONPs were measured and correlated with IONP concentration. Unlike relaxation data, magnetic susceptibility was independent of whether IONPs were free or internalized, making it an excellent candidate for IONP quantification. Using IONP concentration derived from mass spectroscopy and measured relaxation times, free and internalized IONP fractions were accurately calculated. Magnetic susceptibility was shown to be a robust technique to measure IONP concentration in this preliminary study. Novel imaging‐based susceptibility mapping techniques could prove to be valuable tools to quantify IONP concentration directly by MRI, for samples of arbitrary shape. Combined with relaxation time mapping techniques, especially T₂ and T₂*, this could be an efficient way to measure both IONP concentration and the internalized IONP fraction in vivo using MRI, to gain insight into tissue function and molecular imaging paradigms. Copyright © 2012 John Wiley & Sons, Ltd.     

How to assess cytotoxicity of (iron oxide‐based) nanoparticles. A technical note using cationic magnetoliposomes

The range of different types of nanoparticles and their biomedical applications is rapidly growing, creating a need to thoroughly examine the effects these particles have on biological entities. One of the most commonly used nanoparticle types is iron oxide nanoparticles, which can be used as MRI contrast agents. The main research topic is the in vitro labeling of cells with iron oxide nanoparticles to render the cells detectable for MRI upon in vivo transplantation. For the correct evaluation of cell function and behavior in vivo, any effects of the nanoparticles on the cells must be completely ruled out. The present work provides a technical note where a detailed overview is given of several assays that could be useful to determine nanoparticle toxicity. The assays described focus on (i) nanoparticle internalization, (ii) immediate cell toxicity, (iii) cell proliferation, (iv) cell morphology, (v) cell functionality and (vi) cell physiology. Potential pitfalls, appropriate controls and advantages/disadvantages of the different assays are given. The main focus of this work is to provide a detailed guide to help other researchers in the field interested in setting up nanoparticle‐toxicity studies. Copyright © 2010 John Wiley & Sons, Ltd.     

Detection of viability of transplanted beta cells labeled with a novel contrast agent – polyvinylpyrrolidone‐coated superparamagnetic iron oxide nanoparticles by magnetic resonance imaging

Islets can be visualized on MRI by labeling with superparamagnetic contrast agent during the transplantation procedure. However, whether the signal intensity reflects the cell number and cellular viability has not been determined. We used a self‐synthesized novel superparamagnetic contrast agent –polyvinylpyrrolidone‐coated superparamagnetic iron oxide nanoparticles (PVP‐SPIO) – to label β‐TC‐6 cells (a mouse insulinoma cell line) or primary islets with commercial Feridex as a control. The labeling efficiency of two agents was compared by Prussian blue staining, intracellular iron content determination and MR scanning. Cells were exposed to hypoxia, high‐glucose or exogenous H₂O₂ stimulation before/after PVP‐SPIO labeling. Normal and injured cells were also transplanted into renal subcapsule. A clinically used 3.0 T MR scan was performed in vitro and 24 h post‐transplantation to investigate the correlation between cellular viability and signal. Our PVP‐SPIO displayed superior biocompatibility and magnetic properties. All of the cells could be labeled at 100 µg/ml iron concentration after 24 h incubation. At 100 µg/ml iron concentration, 1 × 10⁵ β cells labeled with PVP‐SPIO could already be visualized in vitro by MRI, less than the detection threshold of Feridex. There existed a linear correlation between the number of labeled cells and R₂ value on the T₂‐weighted images. The signal intensity and the intracellular iron content declined along with the decreased viability of labeled cells. There was also a significant difference in signal intensity between injured and normal labeled cells after transplantation. From these results, we concluded that PVP‐SPIO possessed superior cell labeling efficiency, and β cells could be labeled without compromising viability and function. The signal intensity on MRI might be a useful predictor to evaluate the number and the viability of PVP‐SPIO‐labeled cells. Copyright © 2012 John Wiley & Sons, Ltd.     

Superparamagnetic iron oxide nanoparticles for direct labeling of stem cells and in vivo MRI tracking

To develop effective stem cell therapies, it is important to track therapeutic cells non‐invasively and monitor homing to areas of pathology. The purpose of this study was to 1 design and evaluate the labeling efficiency of commercially available dextran‐coated superparamagnetic iron oxide nanoparticles, FeraTrack Direct (FTD), in various stem and immune cells; 2 assess the cytotoxicity and tolerability of the FTD in stem cells; and 3 monitor stem cell homing using FTD‐labeled bone‐marrow‐derived mesenchymal stromal cells (BMSCs) and neural stem cells (NSCs) in a tumor model by in vivo MRI. BMSCs, NSCs, hematopoietic stem cells (HSCs), T‐lymphocytes, and monocytes were labeled effectively with FTD without the need for transfection agents, and Prussian blue (PB) staining and transmission electron microscopy (TEM) confirmed intracellular uptake of the agent. The viability, proliferation, and functionality of the labeled cells were minimally or not affected after labeling. When 10⁶ FTD‐labeled BMSCs or NSCs were injected into C6 glioma bearing nude mice, the cells homing to the tumors were detected as hypointense regions within the tumor using 3 T clinical MRI up to 10 days post injection. Histological analysis confirmed the homing of injected cells to the tumor by the presence of PB positive cells that are not macrophages. Labeling of stem cells or immune cells with FTD was non‐toxic, and should facilitate the translation of this agent to clinical trials for evaluation of trafficking of cells by MRI. Copyright © 2015 John Wiley & Sons, Ltd.     

超顺磁性氧化铁对肝脏MR成像效果的影响

目的 观察超顺磁性氧化铁(SPIO)对肝脏MR成像效果的影响.方法 用化学共沉淀法制备具有肝脏特异性的MR对比剂SPIO,分别将生理盐水、SPIO样品及目前临床广泛使用的Gd-DTPA注入30只大白兔体内,5 min、30 min、60 min后进行MR成像,分别测量肝脏和背部肌肉的信号强度并计算相对信号强度比(相对信号强度比＝肝脏信号强度/肌肉信号强度).结果 Gd-DTPA使肝脏T1WI相对信号强度比(ENH)显著升高,但30 min即开始恢复,持续时间短,SPIO使肝脏T2WI相对信号强度比显著降低,60 min仍能维持高ENH,持续时间长.结论 SPIO具有良好的晶体结构和均匀的纳米尺寸,能显著降低肝脏MR T2WI相对信号强度比,可作为MRI阴性对比剂.     

Variations in labeling protocol influence incorporation,distribution and retention of iron oxide nanoparticles into human umbilical vein endothelial cells

Various studies have shown that various cell types can be labeled with iron oxide particles and visualized by magnetic resonance imaging (MRI). However, reported protocols for cell labeling show a large variation in terms of labeling dose and incubation time. It is therefore not clear how different labeling protocols may influence labeling efficiency. Systematic assessment of the effects of various labeling protocols on labeling efficiency of human umbilical vein endothelial cells (HUVEC) using two different types of iron oxide nanoparticles, i.e. super paramagnetic iron oxide particles (SPIOs) and microparticles of iron oxide (MPIOs), demonstrated that probe concentration, incubation time and particle characteristics all influence the efficiency of label incorporation, label distribution, label retention and cell behavior. For SPIO the optimal labeling protocol consisted of a dose of 12.5 µg iron/2 ml/9.5 cm² and an incubation time of 24 h, resulting in an average iron load of 12.0 pg iron/per cell (uptake efficiency of 9.6%). At 4 h many SPIOs are seen sticking to the outside of the cell instead of being taken up by the cell. For MPIO optimal labeling was obtained with a dose of 50 µg iron/2 ml/9.5 cm². Incubation time was of less importance since most of the particles were already incorporated within 4 h with a 100% labeling efficiency, resulting in an intracellular iron load of 626 pg/cell. MPIO were taken up more efficiently than SPIO and were also better tolerated. HUVEC could be exposed to and contain higher amounts of iron without causing significant cell death, even though MPIO had a much more pronounced effect on cell appearance. Using optimal labeling conditions as found for HUVEC on other cell lines, we observed that different cell types react differently to identical labeling conditions. Consequently, for each cell type separately an optimal protocol has to be established. Copyright © 2010 John Wiley & Sons, Ltd.     

How cellular processing of superparamagnetic nanoparticles affects their magnetic behavior and NMR relaxivity

Cellular processing of nanomaterials may affect their physical properties at the root of various biomedical applications. When nanoparticles interact with living cells, their spatial distribution is progressively modified by cellular activity, which tends to concentrate them into intracellular compartments, changing in turn their responsivity to physical stimuli. In this paper, we investigate the consequences of cellular uptake on the related magnetic properties and NMR relaxivity of iron oxide nanoparticles. The superparamagnetic behavior (field‐dependent and temperature‐dependent magnetization curves investigated by SQUID (Superconducting Quantum Interference Device) measurements) and nuclear magnetic relaxation dispersion (NMRD) R₁ profiles of citrate‐coated maghemite nanoparticles (mean diameter 8 nm) were characterized in colloidal suspension and after being uptaken by several types of cells (tumor cells, stem cells and macrophages). The temperature‐dependent magnetization as well as the NMRD profile were changed following cellular uptake depending on the stage of endocytosis process while the field‐dependent magnetization at room temperature remained unchanged. Magnetic coupling between nanoparticles confined in cell lysosomes accounts for the modification in magnetic behavior, thereby reflecting the local organization of nanoparticles. NMR longitudinal relaxivity was directly sensitive to the intracellular distribution of nanoparticles, in line with Transmission Electron Microscopy TEM observations. This study is the first attempt to link up magnetic properties and NMR characterization of iron oxide nanoparticles before and after their cell processing. Copyright © 2012 John Wiley & Sons, Ltd.     

Assessing cytotoxicity of (iron oxide‐based) nanoparticles: an overview of different methods exemplified with cationic magnetoliposomes

Iron oxide nanoparticles are the most widely used T₂/T₂* contrast agents and for biomedical research purposes, one of the main applications is the in vitro labeling of stem or therapeutic cells, allowing them to be subsequently tracked in vivo upon transplantation. To allow this, the nanoparticles used should not show any sign of cytotoxicity and not affect cellular physiology as this could impede normal cell functionality in vivo or lead to undesired side‐effects. Assessing the biocompatibility of the nanoparticles has proven to be quite a difficult task. In the present work, a small overview of commonly used assays is presented in order to assess several aspects, such as cell viability, induction of reactive oxygen species, nanoparticle uptake, cellular morphology, cellular proliferation, actin cytoskeleton architecture and differentiation of stem cells. The main focus is on comparing the advantages and disadvantages of the different assays, highlighting several common problems and presenting possible solutions to these problems as well as pointing out the high importance of the relationship between intracellular nanoparticle concentration and cytotoxicity. Copyright © 2009 John Wiley & Sons, Ltd.     

Labeling of multiple cell lines using a new iron oxide agent for cell tracking by MRI

Stem cells, cancer cells and immune cells were labeled by co‐incubation with a new ultra‐small iron oxide nanoparticle called Molday ION Rhodamine‐B (MIRB). Iron staining, fluorescence imaging, transmission electron microscopy and flow cytometry were used to assess cell viability, function and labeling efficiency. This study has shown that MIRB can be used to label both adherent and nonadherent cell lines, with high viability and loading levels sufficient for their detection in vivo by MRI at 3 T. Copyright © 2011 John Wiley & Sons, Ltd.     

Covalent coupling of gum arabic onto superparamagnetic iron oxide nanoparticles for MRI cell labeling: physicochemical and in vitro characterization

Gum arabic (GA) is a hydrophilic composite polysaccharide derived from exudates of Acacia senegal and Acacia seyal trees. It is biocompatible, possesses emulsifying and stabilizing properties and has been explored as coating agent of nanomaterials for biomedical applications, namely magnetic nanoparticles (MNPs). Previous studies focused on the adsorption of GA onto MNPs produced by co‐precipitation methods. In this work, MNPs produced by a thermal decomposition method, known to produce uniform particles with better crystalline properties, were used for the covalent coupling of GA through its free amine groups, which increases the stability of the coating layer. The MNPs were produced by thermal decomposition of Fe(acac)₃ in organic solvent and, after ligand‐exchange with meso‐2,3‐dimercaptosuccinic acid (DMSA), GA coating was achieved by the establishment of a covalent bond between DMSA and GA moieties. Clusters of several magnetic cores entrapped in a shell of GA were obtained, with good colloidal stability and promising magnetic relaxation properties (r₂/r₁ ratio of 350). HCT116 colorectal carcinoma cell line was used for in vitro cytotoxicity evaluation and cell‐labeling efficiency studies. We show that, upon administration at the respective IC₅₀, GA coating enhances MNP cellular uptake by 19 times compared to particles bearing only DMSA moieties. Accordingly, in vitro MR images of cells incubated with increasing concentrations of GA‐coated MNP present dose‐dependent contrast enhancement. The obtained results suggest that the GA magnetic nanosystem could be used as a MRI contrast agent for cell‐labeling applications. Copyright © 2015 John Wiley & Sons, Ltd.     

Electron paramagnetic resonance as a sensitive tool to assess the iron oxide content in cells for MRI cell labeling studies

MRI cell tracking is a promising technique to track various cell types (stem cells, tumor cells, etc.) in living animals. Usually, cells are incubated with iron oxides (T₂ contrast agent) in order to take up the particles before being injected in vivo. Iron oxide quantification is important in such studies for validating the labeling protocols and assessing the dilution of the particles with cell proliferation. We here propose to implement electron paramagnetic resonance (EPR) as a very sensitive method to quantify iron oxide concentration in cells. Iron oxide particles exhibit a unique EPR spectrum, which directly reflects the number of particles in a sample. In order to compare EPR with existing methods (Perls's Prussian blue reaction, ICP‐MS and fluorimetry), we labeled tumor cells (melanoma and renal adenocarcinoma cell lines) and fibroblasts with fluorescent iron oxide particles, and determined the limits of detection of the different techniques. We show that EPR is a very sensitive technique and is specific for iron oxide quantification as measurements are not affected by endogenous iron. As a consequence, EPR is well adapted to perform ex vivo analysis of tissues after cell tracking experiments in order to confirm MRI results. Copyright © 2012 John Wiley & Sons, Ltd.     

Efficient transfection of MG‐63 osteoblasts using magnetic nanoparticles and oscillating magnetic fields

Aims: To examine the potential of magnetic nanoparticles (MNPs) in transfecting human osteosarcoma fibroblasts (MG‐63) and investigate the effects of a novel non‐viral oscillating nanomagnetic gene transfection system (magnefect‐nano?) in enhancing transfection efficiency (TE). Methods: MG‐63 cells were transfected using MNPs coupled with a GFP‐carrying plasmid. The magnefect‐nano system was evaluated for transfection efficiency and potential associated effects on cell viability. Results: MG‐63 cells were efficiently transfected using MNPs and the magnefect‐nano system significantly enhanced overall transfection efficiency. MNPs were not found to affect cell viability and/or function of the cells. Conclusion: Non‐viral transfection using MNPs and the magnefect‐nano system can be used to transfect MG‐63 cells and assist reporter gene delivery on a single cell basis, highlighting the wide potential of nanomagnetic gene transfection in gene therapy. Copyright © 2012 John Wiley & Sons, Ltd.     

Magnetic labeling of non‐phagocytic adherent cells with iron oxide nanoparticles: a comprehensive study

Small particles of iron oxide (SPIO) and ultrasmall particles of iron oxide (USPIO), inducing a strong negative contrast on T₂ and T₂*‐weighted MR images, are the most commonly used systems for the magnetic labeling of cultured cells and their subsequent detection by magnetic resonance imaging (MRI). The purpose of this work is to study the influence of iron incubation concentration, nanoparticle size and nanoparticle coating on the magnetic labeling and the viability of non‐phagocytic adherent cells in culture. The magnetic labeling of 3T6 fibroblasts was studied by T₂‐weighted MRI at 4.7 T and by dosing—or cytochemical revealing—of iron through methods based on Perl's Prussian blue staining. Cells were incubated for 48 h with increasing iron concentrations of SPIO (25–1000 µg Fe/ml Endorem®). Sinerem®, a USPIO (20–40 nm) coated with neutral dextran, and Resovist® (65 nm), a SPIO bearing an anionic carboxydextran coating, were compared with Endorem® (dextran‐coated, 80–150 nm) as magnetic tags. The iron loading of marrow stromal cell primary cultures (MSCs) isolated from rat femurs was compared with that of 3T6 fibroblasts. The SPIO‐labeling of cells with Endorem® was found to be dependent on the iron incubation concentration. MSCs, more sparsely distributed in the culture, exhibited higher iron contents than more densely populated 3T6 fibroblast cultures. A larger iron loading was achieved with Resovist® than with Endorem®, which in turn was more efficient than Sinerem® as a magnetic tag. The magnetic labeling of cultured non‐phagocytic adherent cells with iron oxide nanoparticles was thus found to be dependent on the relative concentration of the magnetic tag and of the cells in culture, on the nanoparticle size, and on the coating type. The viability of cells, estimated by methods assessing cell membrane permeability, was not affected by magnetic labeling in the conditions used in this work. Copyright © 2008 John Wiley & Sons, Ltd.     

超顺磁性纳米氧化铁颗粒标记胰腺癌细胞的MR分子成像

目的 探讨超顺磁性纳米氧化铁颗粒（SPION）靶向标记胰腺癌细胞（BxPC-3）行MR分子成像的可行性。方法 制备黏蛋白1（MUC1）靶向修饰的探针MUC1-SPION（靶向组）,并以牛血清蛋白（BSA）制备非靶向探针BSA-SPION（非靶向组）。采过噻唑蓝（MTT）法测试不同MUC1-SPION浓度下（铁浓度为0、6.25、12.50、25、50、100、200 μg/ml）的细胞毒性。并分别于铁浓度为50、100、200 μg/ml条件下,对靶向组及对照组与BxPC-3细胞共同孵育2 h后的细胞悬液进行MR成像,测定横向弛豫时间（T2）,计算T2强化率。以普鲁士蓝染色观察靶向探针与细胞结合情况。结果 MTT法细胞毒性实验显示,不同MUC1-SPION浓度下BXPC-3细胞增殖率差异无统计学意义（F=1.74,P=0.183）。铁浓度50、100、200 μg/ml条件下,2组间T2值和T2强化率的差异均有统计学意义（P均<0.05）。普鲁士蓝染色显示靶向组的蓝染颗粒更多。结论 MUC1-SPION对BxPC-3细胞具有良好的靶向性,以SPION靶向标记BxPC-3细胞进行MRI安全、可行。     

超顺磁性氧化铁纳米粒子在脑磁共振成像中的应用

超顺磁性氧化铁纳米粒子的磁性及生物相容性,使其在生物医学多个领域的应用研究都逐渐发展起来。本文介绍磁共振成像（MRI）及脑功能磁共振成像（fMRI）基本原理。列举不同性能的磁性氧化铁粒子作为磁共振成像对比剂在脑科学应用中的研究进展。表面结合单克隆抗体、蛋白质、多肽、核苷酸分子或其它特殊聚合物的磁性氧化铁粒子具有吸收特异性（靶向性）,结合MRI可实现对脑部病变前期改变、药物输运及治疗的监测,对细胞、生物分子包括mRNA的成像及探测。经葡聚糖或聚乙二醇修饰的超顺磁性氧化铁纳米粒子血液半衰期较长,可作为对比剂用于脑fMRI成像。控制氧化铁纳米粒子的粒度及表面修饰物的物理化学性质、提高饱和磁化强度、借以接枝以各种靶向性的物质、开发具有荧光-磁性等多种性能的复合纳米粒子及掌握纳米粒子与生物分子、细胞、及生物组织之间的相互作用,则需要更深入的研究。     

Properties and suspension stability of dendronized iron oxide nanoparticles for MRI applications

Functionalized iron oxide nanoparticles have attracted an increasing interest in the last 10 years as contrast agents for MRI. One challenge is to obtain homogeneous and stable aqueous suspensions of iron oxide nanoparticles without aggregates. Iron oxide nanoparticles with sizes around 10 nm were synthesized by two methods: the particle size distribution in water suspension of iron oxide nanoparticles synthesized by the co‐precipitation method was improved by a process involving two steps of ligand exchange and phase transfer and was compared with that of iron oxide nanoparticles synthesized by thermal decomposition and functionalized by the same dendritic molecule. The saturation magnetization of dendronized nanoparticles synthesized by thermal decomposition was lower than that of nanoparticles synthesized by co‐precipitation. The r₂ relaxivity values were shown to decrease with the agglomeration state in suspension and high r₂ values and r₂/r₁ ratios were obtained with nanoparticles synthesized by co‐precipitation by comparison with those of commercial products. Dendronized iron oxide nanoparticles thus have potential properties as contrast agent. Copyright © 2010 John Wiley & Sons, Ltd.     

Surface functionalization of magnetic iron oxide nanoparticles for MRI applications – effect of anchoring group and ligand exchange protocol

Hydrophobic magnetite nanoparticles synthesized from thermal decomposition of iron salts must be rendered hydrophilic for their application as MRI contrast agents. This process requires refunctionalizing the surface of the nanoparticles with a hydrophilic organic coating such as polyethylene glycol. Two parameters were found to influence the magnetic behavior and relaxivity of the resulting hydrophilic iron oxide nanoparticles: the functionality of the anchoring group and the protocol followed for the functionalization. Nanoparticles coated with PEGs via a catecholate‐type anchoring moiety maintain the saturation magnetization and relaxivity of the hydrophobic magnetite precursor. Other anchoring functionalities, such as phosphonate, carboxylate and dopamine decrease the magnetization and relaxivity of the contrast agent. The protocol for functionalizing the nanoparticles also influences the magnetic behavior of the material. Nanoparticles refunctionalized according to a direct biphasic protocol exhibit higher relaxivity than those refunctionalized according to a two‐step procedure which first involves stripping the nanoparticles. This research presents the first systematic study of both the binding moiety and the functionalization protocol on the relaxivity and magnetization of water‐soluble coated iron oxide nanoparticles used as MRI contrast agents. Copyright © 2010 John Wiley & Sons, Ltd.     

Stem cell labeling for magnetic resonance imaging

In vivo applications of cells for the monitoring of their cell dynamics increasingly use non‐invasive magnetic resonance imaging. This imaging modality allows in particular to follow the migrational activity of stem cells intended for cell therapy strategies. All these approaches require the prior labeling of the cells under investigation for excellent contrast against the host tissue background in the imaging modality. The present review discusses the various routes of cell labeling and describes the potential to observe both cell localization and their cell‐specific function in vivo. Possibilities for labeling strategies, pros and cons of various contrast agents are pointed out while potential ambiguities or problems of labeling strategies are emphasized.     

Polyglycerol‐grafted superparamagnetic iron oxide nanoparticles: highly efficient MRI contrast agent for liver and kidney imaging and potential scaffold for cellular and molecular imaging

Polyglycerol as a water‐soluble and biocompatible hyperbranched polymer was covalently grafted on the surface of superparamagnetic iron oxide nanoparticles. With this aim, superparamagnetic magnetite nanoparticles were prepared by coprecipitation in aqueous media, then the surface of nanoparticles was modified to introduce the reactive groups on the surface of nanoparticles. After that, polyglycerol was grafted on the surface of nanoparticles by ring‐opening anionic polymerization of glycidol using n‐bulyllithium as initiator. The magnetometry, relaxometry and phantom MRI experiments of this highly stable ferrofluid showed its high potential as a negative MRI contrast agent. Calculated r₁ and r₂ relaxivities at different magnetic fields were higher than the values reported for commercially available iron oxide contrast agents. The in vivo MRI studies showed that, after intravenous injection into mice, the particles produced a strong negative contrast in liver and kidneys, which persisted for 80 min (in liver) to 110 min (in kidneys). The negative contrast of the liver and kidneys weakened over the time, suggesting that polyglycerol coating renders the nanoparticles stealth and possibly optimal for renal excretion. Copyright © 2012 John Wiley & Sons, Ltd.     

Uniform mesoporous silica coated iron oxide nanoparticles as a highly efficient,nontoxic MRI T2 contrast agent with tunable proton relaxivities

Monodisperse mesoporous silica (mSiO₂) coated superparamagnetic iron oxide (Fe₃O₄@mSiO₂) nanoparticles (NPs) have been developed as a potential magnetic resonance imaging (MRI) T₂ contrast agent. To evaluate the effect of surface coating on MRI contrast efficiency, we examined the proton relaxivities of Fe₃O₄@mSiO₂ NPs with different coating thicknesses. It was found that the mSiO₂ coating has a significant impact on the efficiency of Fe₃O₄ NPs for MRI contrast enhancement. The efficiency increases with the thickness of mSiO₂ coating and is much higher than that of the commercial contrast agents. Nuclear magnetic resonance (NMR) relaxometry of Fe₃O₄@mSiO₂ further revealed that mSiO₂ coating is partially permeable to water molecules and therefore induces the decrease of longitudinal relaxivity, r₁. Biocompatibility evaluation of various sized (ca. 35–95 nm) Fe₃O₄@mSiO₂ NPs was tested on OC‐k3 cells and the result showed that these particles have no negative impact on cell viability. The enhanced MRI efficiency of Fe₃O₄@mSiO₂ highlights these core–shell particles as highly efficient T₂ contrast agents with high biocompatibility. Copyright © 2012 John Wiley & Sons, Ltd.