Matrix-dependent size modifications of iron oxide nanoparticles (Ferumoxytol) spiked into rat blood cells and plasma: Characterisation with TEM, AF4-UV-MALS-ICP-MS/MS and spICP-MS

Kenneth C Nwoko; Andrea Raab; Lesley Cheyne; Dana Dawson; Eva Krupp; Jörg Feldmann

doi:10.1016/j.jchromb.2019.06.029

Matrix-dependent size modifications of iron oxide nanoparticles (Ferumoxytol) spiked into rat blood cells and plasma: Characterisation with TEM, AF4-UV-MALS-ICP-MS/MS and spICP-MS

Kenneth C Nwoko^* (Corresponding Author), Andrea Raab, Lesley Cheyne, Dana Dawson, Eva Krupp, Jörg Feldmann

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

Engineered nanoparticles such as iron oxide (Fe3O4) nanoparticles (IONPs) offer several benefits in nanomedicine, notably as contrast agents in magnetic resonance imaging (MRI). Ferumoxytol, a suspension of IONPs (with a manufacturer's reported particle diameter of 27 nm-30 nm) was characterized as a standard by spiking into rat blood plasma and cell fractions. Nanoparticle separation, and characterisation was investigated with asymmetric flow field-flow fractionation (AF4) coupled online to ultraviolet-visible spectroscopy (UV-VIS), multi-angle light scattering (MALS) and inductively coupled plasma mass spectrometry (ICP-MS) detectors; also with single particle inductively coupled plasma mass spectrometry (spICP-MS) and transmission electron microscopy (TEM). MALS signal of pristine Ferumoxytol indicated radii of gyration (Rg) between 15 and 28 nm for the Fe-containing fraction and 30-75 nm for the non-Fe fraction. IONPs spiked into blood plasma indicated a polydisperse distribution between 40 nm - 120 nm suggesting matrix-induced size alterations. Spiking of the IONPs into cells showed a shift in ICP-MS Fe signal to 15 min, however the MALS signal was undetected within the Fe containing fraction of the IONPs suggesting NP loss due to membrane-particle attraction. spICP-MS analysis of IONPs spiked in rat plasma suggested the release of Fe-containing colloids into plasma causing an increase in diameter of IONPs to 52 ± 0.8 nm; whereas no major variation in particle size and distribution of the IONPs spiked in cell fractions was observed (33.2 ± 2.0 nm) suggesting non-alteration of the NP Fe core. A complementary application of microscopic, light scattering, and mass spectrometry techniques for the characterisation of NPs in challenging biological matrices like blood has been demonstrated.

Original language	English
Pages (from-to)	356-365
Number of pages	10
Journal	Journal of Chromatography B
Volume	1124
Early online date	24 Jun 2019
DOIs	https://doi.org/10.1016/j.jchromb.2019.06.029
Publication status	Published - 15 Aug 2019

Bibliographical note

KN gratefully acknowledges the University of Aberdeen for an Elphinstone Ph.D. studentship and the Niger Delta Development Commission (NDDC) for a research grant (RG-13451-10). The authors also gratefully acknowledge Postnova Analytics UK especially Dr. Bassem Sabagh for the loan of the AF4 system together with training, support, and advice on the technique. Microscopy was performed at the Microscopy and Histology Core facility, University of Aberdeen.

Keywords

Ferumoxytol
Nanoparticles
Blood
Plasma
Cells

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Matrix-dependent size modifications of iron oxide nanoparticles (Ferumoxytol) spiked into rat blood cells and plasma: Characterisation with TEM, AF4-UV-MALS-ICP-MS/MS and spICP-MS. / Nwoko, Kenneth C (Corresponding Author); Raab, Andrea; Cheyne, Lesley et al.
In: Journal of Chromatography B, Vol. 1124, 15.08.2019, p. 356-365.

Research output: Contribution to journal › Article › peer-review

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abstract = "Engineered nanoparticles such as iron oxide (Fe3O4) nanoparticles (IONPs) offer several benefits in nanomedicine, notably as contrast agents in magnetic resonance imaging (MRI). Ferumoxytol, a suspension of IONPs (with a manufacturer's reported particle diameter of 27 nm-30 nm) was characterized as a standard by spiking into rat blood plasma and cell fractions. Nanoparticle separation, and characterisation was investigated with asymmetric flow field-flow fractionation (AF4) coupled online to ultraviolet-visible spectroscopy (UV-VIS), multi-angle light scattering (MALS) and inductively coupled plasma mass spectrometry (ICP-MS) detectors; also with single particle inductively coupled plasma mass spectrometry (spICP-MS) and transmission electron microscopy (TEM). MALS signal of pristine Ferumoxytol indicated radii of gyration (Rg) between 15 and 28 nm for the Fe-containing fraction and 30-75 nm for the non-Fe fraction. IONPs spiked into blood plasma indicated a polydisperse distribution between 40 nm - 120 nm suggesting matrix-induced size alterations. Spiking of the IONPs into cells showed a shift in ICP-MS Fe signal to 15 min, however the MALS signal was undetected within the Fe containing fraction of the IONPs suggesting NP loss due to membrane-particle attraction. spICP-MS analysis of IONPs spiked in rat plasma suggested the release of Fe-containing colloids into plasma causing an increase in diameter of IONPs to 52 ± 0.8 nm; whereas no major variation in particle size and distribution of the IONPs spiked in cell fractions was observed (33.2 ± 2.0 nm) suggesting non-alteration of the NP Fe core. A complementary application of microscopic, light scattering, and mass spectrometry techniques for the characterisation of NPs in challenging biological matrices like blood has been demonstrated.",

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AU - Nwoko, Kenneth C

AU - Raab, Andrea

AU - Cheyne, Lesley

AU - Dawson, Dana

AU - Krupp, Eva

AU - Feldmann, Jörg

N1 - KN gratefully acknowledges the University of Aberdeen for an Elphinstone Ph.D. studentship and the Niger Delta Development Commission (NDDC) for a research grant (RG-13451-10). The authors also gratefully acknowledge Postnova Analytics UK especially Dr. Bassem Sabagh for the loan of the AF4 system together with training, support, and advice on the technique. Microscopy was performed at the Microscopy and Histology Core facility, University of Aberdeen.

PY - 2019/8/15

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N2 - Engineered nanoparticles such as iron oxide (Fe3O4) nanoparticles (IONPs) offer several benefits in nanomedicine, notably as contrast agents in magnetic resonance imaging (MRI). Ferumoxytol, a suspension of IONPs (with a manufacturer's reported particle diameter of 27 nm-30 nm) was characterized as a standard by spiking into rat blood plasma and cell fractions. Nanoparticle separation, and characterisation was investigated with asymmetric flow field-flow fractionation (AF4) coupled online to ultraviolet-visible spectroscopy (UV-VIS), multi-angle light scattering (MALS) and inductively coupled plasma mass spectrometry (ICP-MS) detectors; also with single particle inductively coupled plasma mass spectrometry (spICP-MS) and transmission electron microscopy (TEM). MALS signal of pristine Ferumoxytol indicated radii of gyration (Rg) between 15 and 28 nm for the Fe-containing fraction and 30-75 nm for the non-Fe fraction. IONPs spiked into blood plasma indicated a polydisperse distribution between 40 nm - 120 nm suggesting matrix-induced size alterations. Spiking of the IONPs into cells showed a shift in ICP-MS Fe signal to 15 min, however the MALS signal was undetected within the Fe containing fraction of the IONPs suggesting NP loss due to membrane-particle attraction. spICP-MS analysis of IONPs spiked in rat plasma suggested the release of Fe-containing colloids into plasma causing an increase in diameter of IONPs to 52 ± 0.8 nm; whereas no major variation in particle size and distribution of the IONPs spiked in cell fractions was observed (33.2 ± 2.0 nm) suggesting non-alteration of the NP Fe core. A complementary application of microscopic, light scattering, and mass spectrometry techniques for the characterisation of NPs in challenging biological matrices like blood has been demonstrated.

AB - Engineered nanoparticles such as iron oxide (Fe3O4) nanoparticles (IONPs) offer several benefits in nanomedicine, notably as contrast agents in magnetic resonance imaging (MRI). Ferumoxytol, a suspension of IONPs (with a manufacturer's reported particle diameter of 27 nm-30 nm) was characterized as a standard by spiking into rat blood plasma and cell fractions. Nanoparticle separation, and characterisation was investigated with asymmetric flow field-flow fractionation (AF4) coupled online to ultraviolet-visible spectroscopy (UV-VIS), multi-angle light scattering (MALS) and inductively coupled plasma mass spectrometry (ICP-MS) detectors; also with single particle inductively coupled plasma mass spectrometry (spICP-MS) and transmission electron microscopy (TEM). MALS signal of pristine Ferumoxytol indicated radii of gyration (Rg) between 15 and 28 nm for the Fe-containing fraction and 30-75 nm for the non-Fe fraction. IONPs spiked into blood plasma indicated a polydisperse distribution between 40 nm - 120 nm suggesting matrix-induced size alterations. Spiking of the IONPs into cells showed a shift in ICP-MS Fe signal to 15 min, however the MALS signal was undetected within the Fe containing fraction of the IONPs suggesting NP loss due to membrane-particle attraction. spICP-MS analysis of IONPs spiked in rat plasma suggested the release of Fe-containing colloids into plasma causing an increase in diameter of IONPs to 52 ± 0.8 nm; whereas no major variation in particle size and distribution of the IONPs spiked in cell fractions was observed (33.2 ± 2.0 nm) suggesting non-alteration of the NP Fe core. A complementary application of microscopic, light scattering, and mass spectrometry techniques for the characterisation of NPs in challenging biological matrices like blood has been demonstrated.

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Matrix-dependent size modifications of iron oxide nanoparticles (Ferumoxytol) spiked into rat blood cells and plasma: Characterisation with TEM, AF4-UV-MALS-ICP-MS/MS and spICP-MS

Abstract

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Keywords

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