Examples of ICP-MS Studies Undertaken by the MS unit based at FWB.
1. Distribution of iron, copper and zinc in serum samples from patients
suffering from various “iron overload” diseases.
Figure 1. The binding of iron to citrate and albumin.
Chromatograms representing the elution of
56
Fe after a gel filtration chromatography as
detected by ICP-MS. Peaks with elution times between 15 and 22 min correspond to the
elution of albumin-bound iron, peaks appearing after 28 min arise from small molecular
weight iron-citrate complexes. (A) Solution containing 10μM Fe, 100μM citrate and 150mM
NaCl. (B) Solution containing 40g/l albumin, 10μM Fe, 100μM citrate and 150mM NaCl. (C)
Soultion with 40g/l oxidised albumin, 10μM Fe, 100μM citrate and 150mM NaCl. All
samples contained 100mM MOPS buffer at pH=7.4. Research grade recombinant human
albumin was used throughout and was a gift from Novozymes Biopharma UK Ltd. Oxidised
albumin was prepared as described by Silva et al. Biochim. Biophys. Acta 1794, 1449.
Figure 2. The distribution of iron in serum samples.
Chromatograms representing the elution of
56
Fe after a gel filtration chromatography as
detected by ICP-MS. Peaks with elution times between 14 and 20 min correspond to ferritin
and transferrin, peaks appearing after 28 min arise from low molecular weight iron complexes.
(A) Normal serum. (B) Thalassaemia major serum, patient was not undergoing chelation
therapy. (C) Thalassaemia major serum, patient receiving subcutaneous desferrioxamine.
Serum samples were provided by Professor Swee Lay Thein of King’s College Hospital.
Figure 3. Copper distribution in sera of (NS) normal healthy individuals, (DM) diabetes type I,
(TM) β-thalassaemia major, (HH) untreated hereditary haemochromatosis, (POD)
paracetamol overdose.
Figure 4. Zinc distribution in sera of (NS) normal healthy individuals, (DM) diabetes type I,
(TM) β-thalassaemia major, (HH) untreated hereditary haemochromatosis, (POD) paracetamol
overdose.
References:
Hider, R.C., Silva, A., Podinovskaia, M., Ma, Y. (2010) Monitoring the efficiency of
chelation therapy: the potential of non transferrin-bound iron. Anal. New York Acad. Sci.
impress.
Silva, A.M.N., Hider, R.C. (2009) Influence of non-enzymatic post-translation modifications
on the ability of human serum albumin to bind iron. Implications for non-transferrin-bound
iron speciation. Biochim. Biophys. Acta 1794, 1449-1458.
Influence of Clioquinol on Fly Brain Iron Levels.
Figure 1. The iron-chelating compound clioquinol was added to the fly food at final
concentrations of 2, 20 and 200 μM and its effects on the Aβ-associated longevity phenotype
and the accumulation of iron in the fly brain was assessed. The median lifespan of flies
expressing Aβ1–40 (a, circles) was not significantly increased by clioquinol at any
concentration; however, flies expressing Arctic Aβ1–42 demonstrated a clear concentrationrelated increase in median survival (a, diamonds). Wild-type Aβ1–42 flies exhibited an
intermediate, but significant, response (a, triangles). Kaplan–Meier survival statistics with the
log rank test were used to analyse the data (significance of difference from no-clioquinol
control, **P < 0.01, ***P < 0.001, unlabelled P > 0.05). Flies expressing Arctic Aβ1–42 (b,
triangles) accumulated significantly more iron in their brains than control flies (b, circles) and
this was only reversed by treatment with 200 μM clioquinol. Error bars show the SD (n = 3).
The significance of the difference between clioquinol-treated and non-treated flies was
calculated pairwise using the two-tailed Student’s t-test (**P < 0.01).
Reference:
Rival, T., Page, R.M., Chandraratna, D.S., Sendall, T.J., Ryder, E., Liu, B., Lewis, H., Rosahl,
T., Hider, R., Camargo, L.M., Shearman, M.S., Crowther, D.C., Lomas. D.A. (2009) Fenton
chemistry and oxidative stress mediate the toxicity of the beta-amyloid peptide in a
Drosophila model of Alzheimer's disease. Eur. J. Neurosci., 29, 1335-1347.
2. Tumour targeting of functionalized Quantum Dot-Liposomes
Dot-Liposomes
Cd2+ quantified by ICP-MS
Figure 1. Schematic diagram showing the structure of f-QD (left), and f-QD-L hybrid vesicles
consisting of cationic (middle) and PEGylated (right) lipids (not drawn to scale). The size,
polydispersity index and zeta potential of f-QD and f-QD-L hybrids used in this study are
depicted.
Figure 2. Biodistribution of different QD nanoparticles in tumor-bearing C57BL6 mice after
intravenous
administration.
(A)
Blood
clearance
profile
of
f-QD,
cationic
f-QD-L
(DOPC:Chol:DOTAP), “fluid” PEGylated f-QD-L (DOPC:Chol:DSPE-PEG2000) and “rigid”
PEGylated f-QD-L (DSPC:Chol:DSPE-PEG2000) hybrids in tumor-bearing C57BL6 mice after tail
vein injection. Tissue biodistribution of above-mentioned nanoparticles at (B) 4 h; (C) 24 h; and
(D) 72 h post tail vein injection. (E) Tumor accumulation of f-QD and f-QD-L hybrids consisting
of DOPC:Chol:DOTAP; DOPC:Chol:DSPE-PEG2000; and DSPC:Chol:DSPE-PEG2000) in B16F10
melanoma bearing animals at 4, 24 and 72 h postinjection. QD concentrations in the tissues were
determined by ICP-MS (n = 4 ± SD). Statistical analysis was performed between f-QD-L
(DOPC:Chol:DOTAP) and f-QD-L (DOPC:Chol:DSPE-PEG2000) hybrids, p value was statistically
significant *** (p < 0.001), * (p < 0.05).
References:
Al-Jamal, W.T., Al-Jamal, K.T., Tian, B., Cakebread, A., Halket, J.M., Kostarelos, K.
(2009) Tumor Targeting of Functionalized Quantum Dot−Liposome Hybrids by Intravenous
Administration. Mol. Pharmaceutics, 6, 520–530.
Al-Jamal, W.T., Al-Jamal, K.T., Cakebread, A., Halket, J.M., Kostarelos, K. (2009) Blood
Circulation and Tissue Biodistribution of Lipid−Quantum Dot (L-QD) Hybrid Vesicles
Intravenously Administered in Mice. Bioconjugate Chem., 20, 1696–1702.