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Intracellular performance of tailored nanoparticle tracers in magnetic particle imaging.

ABSTRACT: Magnetic Particle Imaging (MPI) is a quantitative mass-sensitive, tracer-based imaging technique, with potential applications in various cellular imaging applications. The spatial resolution of MPI, in the first approximation, improves by decreasing the full width at half maximum (FWHM) of the field-derivative of the magnetization, dm/dH of the nanoparticle (NP) tracers. The FWHM of dm/dH depends critically on NPs' size, size distribution, and their environment. However, there is limited information on the MPI performance of the NPs after their internalization into cells. In this work, 30 to 150 μg of the iron oxide NPs were incubated in a lysosome-like acidic buffer (0.2 ml, 20 mM citric acid, pH 4.7) and investigated by vibrating sample magnetometry, magnetic particle spectroscopy, transmission electron microscopy, and dynamic light scattering (DLS). The FWHM of the dm/dH curves of the NPs increased with incubation time and buffer to NPs ratio, consistent with a decrease in the median core size of the NPs from ∼20.1 ± 0.98 to ∼18.5 ± 3.15 nm. Further, these smaller degraded NPs formed aggregates that responded to the applied field by hysteretic reversal at higher field values and increased the FWHM. The rate of core size decrease and aggregation were inversely proportional to the concentration of the incubated NPs, due to their slower biodegradation kinetics. The results of this model experiment show that the MPI performance of the NPs in the acidic environments of the intracellular organelles (i.e., lysosomes and endosomes) can be highly dependent on their rate of internalization, residence time, and degradation.

SUBMITTER: Arami H

PROVIDER: S-EPMC3977802 | biostudies-other | 2014 May

REPOSITORIES: biostudies-other

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Project description:Magnetic particle imaging (MPI) is a recently developed imaging technique that seeks to provide ultrahigh resolution and tracer sensitivity with positive contrast directly originated from superparamagnetic iron oxide nanoparticles (NPs). MPI signals can be generated from a combination of Néel relaxation, Brownian rotational diffusion, and hysteretic reversal mechanisms of NPs in response to applied magnetic fields. When specific targeting of organs, such as carcinoma and endothelial cardiovascular cells, is needed, different behavior may be expected in immobilized NPs, due to complete or partial elimination of the Brownian motion. Here, the authors present an experimental investigation of the MPI spatial resolution and signal intensities as a function of a wide range of median core sizes of NPs under four representative conditions, including after immobilization in a tissue equivalent medium.Monodisperse hydrophobic NPs with median core diameters (d0) ranging from 7 to 22 nm were synthesized in organic media and subsequently dispersed in aqueous solution after a facile surface modification. Morphology, median size, size distribution, and magnetic properties of the NPs were investigated. Hydrophobic and hydrophilic NPs with various core sizes were immobilized in trioctyl phosphine oxide and agarose gel, respectively. Their size-dependent performance as MPI tracers for system matrix and x-space image reconstruction was evaluated using magnetic particle spectrometry (MPS) and compared with the free rotating counterparts.Immobilized NPs with core diameters smaller than ≈ 20 nm have similar spatial resolution, but lower signal intensities when compared with their free rotating counterparts. Compared to their performance in solution, spatial resolution was improved, but signal intensity was lower, when larger NPs with core size of 22 nm were immobilized in agarose. Same trends were observed in signal intensities, when considering either system matrix or x-space approaches. The harmonic and dm/dH signal intensities changed linearly and the spatial resolution did not change with decreasing NP concentration up to 15 μg/ml.The results show that the MPI signal is very sensitive to both NP size and environment. The authors' calculations show that Brownian rotational diffusion is slower than the field switching cycle and, therefore, it has minimal influence on MPS signals. dm/dH analyses show that Néel relaxation is the dominant mechanism determining MPI response in smaller NPs (d0 < ≈ 20 nm). Larger NPs show hysteretic reversal when the applied field amplitude is large enough to overcome the coercivity. Linear variation of the MPS signal intensity with iron concentration but with uniform spatial resolution enables quantitative imaging for a range of applications, from high-concentration bolus chase imaging to low-concentration molecular imaging (while the authors' instrument is noise-limited to ≈ millimolar iron concentrations, nanomolar sensitivity is expected for MPI, theoretically). These results pave the way for future application of the authors' synthesized tracers for immobilized or in vivo targeted MPI of tissues.

Project description:BackgroundIron oxide nanoparticles (IONs) are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI) was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI.Methods and resultsIONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles). Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS) measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem) and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles) bound to blood clots.ConclusionsThe presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular) MPI and warrants further investigation of the FibPep-ION-Micelle platform for in vivo, non-invasive imaging of fibrin in preclinical disease models of thrombus-related pathologies and atherosclerosis.

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Intracellular performance of tailored nanoparticle tracers in magnetic particle imaging.

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