Silica-coated super-paramagnetic iron oxide nanoparticles (SPIONPs): a new type contrast agent of T1 magnetic resonance imaging (MRI)

Author(s): M. Zubair Iqbal ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Xuehua Ma ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Tianxiang Chen ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Ling'e Zhang ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Wenzhi Ren ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Lingchao Xiang ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Aiguo Wu ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵

Publication date (Electronic): 2015

Journal: Journal of Materials Chemistry B

Publisher: Royal Society of Chemistry (RSC)

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Abstract

Silica-coated-SPIONPs- T ₁ enhanced MRI contrast agents.

Abstract

Magnetic resonance imaging (MRI), a sophisticated promising three-dimensional tomographic noninvasive diagnostic technique, has an intrinsic advantage in safety compared with radiotracer and optical imaging modalities; however, MRI contrast agents are less sensitive than complexes used in other imaging techniques. Usually the clinically used Gd-based complexes MRI- T ₁ contrast agents are toxic; therefore, the demand for nontoxic novel T ₁-weighted MRI candidates with ultrasensitive imaging and advanced functionality is very high. In this research, silica-coated ultra-small monodispersed super-paramagnetic iron oxide nanoparticles were synthesized via a thermal decomposition method, which demonstrated themselves as a high performance T ₁-weighted MRI contrast agent for heart, liver, kidney and bladder based on in vivo imaging analyses. Transmission electron microscopy (TEM) results illustrated that the diameter of the SPIONPs was in the range of 4 nm and the average size of Fe ₃O ₄@SiO ₂ was about 30–40 nm. X-ray diffraction (XRD) and Raman spectroscopy analyses revealed the phase purity of the prepared SPIONPs. These magnetite nanoparticles exhibited a weak magnetic moment at room temperature because of the spin-canting effect, which promoted a high positive signal enhancement ability. MTT assays and histological analysis demonstrated good biocompatibility of the SPIONPs in vitro and in vivo. In addition, the silica-coated ultra-small (4 nm sized) magnetite nanoparticles exhibited a good r ₁ relaxivity of 1.2 mM ⁻¹ s ⁻¹ and a low r ₂/ r ₁ ratio of 6.5 mM ⁻¹ s ⁻¹. In vivo T ₁-weighted MR imaging of heart, liver, kidney and bladder in mice after intravenous injection of nanoparticles further verified the high sensitivity and biocompatibility of the as-synthesized magnetite nanoparticles. These results reveal silica-coated SPIONPs as a promising candidate for a T ₁ contrast agent with extraordinary capability to enhance MR images.

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Physical-chemical aspects of protein corona: relevance to in vitro and in vivo biological impacts of nanoparticles.

Marco P Monopoli, Dorota Walczyk, Abigail L. Campbell … (2011)

It is now clearly emerging that besides size and shape, the other primary defining element of nanoscale objects in biological media is their long-lived protein ("hard") corona. This corona may be expressed as a durable, stabilizing coating of the bare surface of nanoparticle (NP) monomers, or it may be reflected in different subpopulations of particle assemblies, each presenting a durable protein coating. Using the approach and concepts of physical chemistry, we relate studies on the composition of the protein corona at different plasma concentrations with structural data on the complexes both in situ and free from excess plasma. This enables a high degree of confidence in the meaning of the hard protein corona in a biological context. Here, we present the protein adsorption for two compositionally different NPs, namely sulfonated polystyrene and silica NPs. NP-protein complexes are characterized by differential centrifugal sedimentation, dynamic light scattering, and zeta-potential both in situ and once isolated from plasma as a function of the protein/NP surface area ratio. We then introduce a semiquantitative determination of their hard corona composition using one-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrospray liquid chromatography mass spectrometry, which allows us to follow the total binding isotherms for the particles, identifying simultaneously the nature and amount of the most relevant proteins as a function of the plasma concentration. We find that the hard corona can evolve quite significantly as one passes from protein concentrations appropriate to in vitro cell studies to those present in in vivo studies, which has deep implications for in vitro-in vivo extrapolations and will require some consideration in the future.

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Iron oxide MR contrast agents for molecular and cellular imaging.

Jeff Bulte, Dara Kraitchman (2004)

Molecular and cellular MR imaging is a rapidly growing field that aims to visualize targeted macromolecules or cells in living organisms. In order to provide a different signal intensity of the target, gadolinium-based MR contrast agents can be employed although they suffer from an inherent high threshold of detectability. Superparamagnetic iron oxide (SPIO) particles can be detected at micromolar concentrations of iron, and offer sufficient sensitivity for T2(*)-weighted imaging. Over the past two decades, biocompatible particles have been linked to specific ligands for molecular imaging. However, due to their relatively large size and clearance by the reticuloendothelial system (RES), widespread biomedical molecular applications have yet to be implemented and few studies have been reproduced between different laboratories. SPIO-based cellular imaging, on the other hand, has now become an established technique to label and detect the cells of interest. Imaging of macrophage activity was the initial and still is the most significant application, in particular for tumor staging of the liver and lymph nodes, with several products either approved or in clinical trials. The ability to now also label non-phagocytic cells in culture using derivatized particles, followed by transplantation or transfusion in living organisms, has led to an active research interest to monitor the cellular biodistribution in vivo including cell migration and trafficking. While most of these studies to date have been mere of the 'proof-of-principle' type, further exploitation of this technique will be aimed at obtaining a deeper insight into the dynamics of in vivo cell biology, including lymphocyte trafficking, and at monitoring therapies that are based on the use of stem cells and progenitors. Copyright (c) 2004 John Wiley & Sons, Ltd.