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Enhanced Efficiency of 13C Dynamic Nuclear Polarization by Superparamagnetic Iron Oxide Nanoparticle Doping.

ABSTRACT: Attainment of high NMR signal enhancements is crucial to the success of in vitro or in vivo hyperpolarized NMR or imaging (MRI) experiments. In this work, we report on the use of a superparamagnetic iron oxide nanoparticle (SPION) MRI contrast agent Feraheme (ferumoxytol) as a beneficial additive in 13C samples for dissolution dynamic nuclear polarization (DNP). Our DNP data at 3.35 T and 1.2 K reveal that addition of 11 mM elemental iron concentration of Feraheme in trityl OX063-doped 3 M [1-13C] acetate samples resulted in a substantial improvement of 13C DNP signal by a factor of almost 3-fold. Concomitant with the large DNP signal increase is the narrowing of the 13C microwave DNP spectra for samples doped with SPION. W-band electron paramagnetic resonance (EPR) spectroscopy data suggest that these two prominent effects of SPION doping on 13C DNP can be ascribed to the shortening of trityl OX063 electron T 1 as explained within the thermal mixing DNP model. Liquid-state 13C NMR signal enhancements as high as 20,000-fold for SPION-doped samples were recorded after dissolution at 9.4 T and 297 K, which is about 3 times the liquid-state NMR signal enhancement of the control sample. While the presence of SPION in hyperpolarized solution drastically reduces 13C T 1, this can be mitigated by polarizing smaller aliquots of DNP samples. Moreover, we have shown that Feraheme nanoparticles (~30 nm in size) can be easily and effectively removed from the hyperpolarized liquid by simple mechanical filtration, thus one can potentially incorporate an in-line filtration for these SPIONS along the dissolution pathway of the hyperpolarizer-a significant advantage over other DNP enhancers such as the lanthanide complexes. The overall results suggest that the commercially-available and FDA-approved Feraheme is a highly efficient DNP enhancer that could be readily translated for use in clinical applications of dissolution DNP.

SUBMITTER: Niedbalski P

PROVIDER: S-EPMC6876865 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Enhanced Efficiency of 13C Dynamic Nuclear Polarization by Superparamagnetic Iron Oxide Nanoparticle Doping.

Niedbalski Peter P Parish Christopher R CR Wang Qing Q Hayati Zahra Z Song Likai L Cleveland Zackary I ZI Lumata Lloyd L

The journal of physical chemistry. C, Nanomaterials and interfaces 20170817 35

Attainment of high NMR signal enhancements is crucial to the success of in vitro or in vivo hyperpolarized NMR or imaging (MRI) experiments. In this work, we report on the use of a superparamagnetic iron oxide nanoparticle (SPION) MRI contrast agent Feraheme (ferumoxytol) as a beneficial additive in 13C samples for dissolution dynamic nuclear polarization (DNP). Our DNP data at 3.35 T and 1.2 K reveal that addition of 11 mM elemental iron concentration of Feraheme in tri ...[more]

PMID: 31768206

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Project description:Superparamagnetic iron oxide nanoparticles (SPION) are employed as diagnostics and therapeutics following intravenous delivery for the treatment of iron deficiency anemia (IDA) in adult patients with chronic kidney failure. Neutrophils are the first defense against blood borne foreign insult and recruit to vascular sites of inflammation via a sequential process that is characterized by adhesive capture, rolling, and shear resistant arrest. A primary chemotactic agonist presented on the glycocalyx of inflamed endothelium is IL-8, which upon binding to its cognate membrane receptor (CXCR1/2) activates a suite of responses in neutrophils. An early response is degranulation with accompanying upregulation of β2-integrin (CD11/CD18) and shedding of L-selectin (CD62L) receptors, which exert differential effects on the efficiency of endothelial recruitment. Feraheme is an FDA approved SPION treatment for IDA, but its effect on the innate immune response of neutrophils during inflammation has not been reported. Here, we studied the immunomodulatory effects of Feraheme on neutrophils freshly isolated from healthy human subjects and stimulated in suspension or on inflammatory mimetic substrates with IL-8. Cells treated with Feraheme exhibited reduced sensitivity to stimulation with IL-8, indicated by reduced upregulation of membrane CD11b/CD18 receptors, high affinity (HA) CD18, and shedding of CD62L. Feraheme also inhibited N-formyl-Met-Leu-Phe (fMLP) induced reactive oxygen species production. Neutrophil rolling, arrest, and migration was assessed in vascular mimetic microfluidic channels coated with E-selectin and ICAM-1 to simulate inflamed endothelium. Neutrophils exposed to Feraheme rolled faster on E-selectin and arrested less frequently on ICAM-1, in a manner dependent upon SPION concentration. Subsequent neutrophil shape change, and migration were also significantly inhibited in the presence of Feraheme. Lastly, Feraheme accelerated clearance of cytosolic calcium flux following IL-8 stimulation. We conclude that uptake of Feraheme by neutrophils inhibits chemotactic activation and downregulates normal rolling to arrest under shear flow. The mechanism involves increased calcium clearance following chemotactic activation, which may diminish the efficiency of recruitment from the circulation at vascular sites of inflammation.

Dataset Information

Enhanced Efficiency of 13C Dynamic Nuclear Polarization by Superparamagnetic Iron Oxide Nanoparticle Doping.

Publications

Enhanced Efficiency of <sup>13</sup>C Dynamic Nuclear Polarization by Superparamagnetic Iron Oxide Nanoparticle Doping.

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