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 | |
| Publication status | Published - 15 Aug 2019 |
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Keywords
- Ferumoxytol
- Nanoparticles
- Blood
- Plasma
- Cells
ASJC Scopus subject areas
- Analytical Chemistry
- Biochemistry
- Clinical Biochemistry
- Cell Biology
Cite this
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; Dawson, Dana; Krupp, Eva; Feldmann, Jörg.
In: Journal of Chromatography B, Vol. 1124, 15.08.2019, p. 356-365.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Matrix-dependent size modifications of iron oxide nanoparticles (Ferumoxytol) spiked into rat blood cells and plasma
T2 - Characterisation with TEM, AF4-UV-MALS-ICP-MS/MS and spICP-MS
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
Y1 - 2019/8/15
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.
KW - Ferumoxytol
KW - Nanoparticles
KW - Blood
KW - Plasma
KW - Cells
UR - https://linkinghub.elsevier.com/retrieve/pii/S1570023219304842
UR - http://www.mendeley.com/research/matrixdependent-size-modifications-iron-oxide-nanoparticles-ferumoxytol-spiked-rat-blood-cells-plasm
UR - http://www.scopus.com/inward/record.url?scp=85068368561&partnerID=8YFLogxK
U2 - 10.1016/j.jchromb.2019.06.029
DO - 10.1016/j.jchromb.2019.06.029
M3 - Article
VL - 1124
SP - 356
EP - 365
JO - Journal of Chromatography B
JF - Journal of Chromatography B
SN - 1570-0232
ER -