TY - JOUR
T1 - Magnetic resonance imaging contrast of iron oxide nanoparticles developed for hyperthermia is dominated by iron content
AU - Wabler, Michele
AU - Zhu, Wenlian
AU - Hedayati, Mohammad
AU - Attaluri, Anilchandra
AU - Zhou, Haoming
AU - Mihalic, Jana
AU - Geyh, Alison
AU - Deweese, Theodore L.
AU - Ivkov, Robert
AU - Artemov, Dmitri
N1 - Funding Information:
Robert Ivkov is an inventor on several issued and pending patents that disclose nanoparticle formulations for imaging and hyperthermia. All patents on which Robert Ivkov is an inventor are assigned to either Johns Hopkins University or Aduro Biotech, LLC. All other authors report no conflicts of interest. This work was funded by an award from the Safeway Foundation and the Prostate Cancer Foundation and by MD TEDCO Maryland Stem Cell Research Fund 2010-MSCRFE-0096. ICP-MS work was supported in part by the Maryland Cigarette Restitution Fund Program at Johns Hopkins Bloomberg School of Public Health and the National Institute of Environmental Health Sciences Center P30 ES00319.
PY - 2014/5
Y1 - 2014/5
N2 - Purpose: Magnetic iron oxide nanoparticles (MNPs) are used as contrast agents for magnetic resonance imaging (MRI) and hyperthermia for cancer treatment. The relationship between MRI signal intensity and cellular iron concentration for many new formulations, particularly MNPs having magnetic properties designed for heating in hyperthermia, is lacking. In this study, we examine the correlation between MRI T2 relaxation time and iron content in cancer cells loaded with various MNP formulations. Materials and methods: Human prostate carcinoma DU-145 cells were loaded with starch-coated bionised nanoferrite (BNF), iron oxide (Nanomag® D-SPIO), Feridex™, and dextran-coated Johns Hopkins University (JHU) particles at a target concentration of 50pg Fe/cell using poly-D-lysine transfection reagent. T2-weighted MRI of serial dilutions of these labelled cells was performed at 9.4T and iron content quantification was performed using inductively coupled plasma mass spectrometry (ICP-MS). Clonogenic assay was used to characterise cytotoxicity. Results: No cytotoxicity was observed at twice the target intracellular iron concentration (∼100pg Fe/cell). ICP-MS revealed highest iron uptake efficiency with BNF and JHU particles, followed by Feridex and Nanomag-D-SPIO, respectively. Imaging data showed a linear correlation between increased intracellular iron concentration and decreased T2 times, with no apparent correlation among MNP magnetic properties. Conclusions: This study demonstrates that for the range of nanoparticle concentrations internalised by cancer cells the signal intensity of T2-weighted MRI correlates closely with absolute iron concentration associated with the cells. This correlation may benefit applications for cell-based cancer imaging and therapy including nanoparticle-mediated drug delivery and hyperthermia.
AB - Purpose: Magnetic iron oxide nanoparticles (MNPs) are used as contrast agents for magnetic resonance imaging (MRI) and hyperthermia for cancer treatment. The relationship between MRI signal intensity and cellular iron concentration for many new formulations, particularly MNPs having magnetic properties designed for heating in hyperthermia, is lacking. In this study, we examine the correlation between MRI T2 relaxation time and iron content in cancer cells loaded with various MNP formulations. Materials and methods: Human prostate carcinoma DU-145 cells were loaded with starch-coated bionised nanoferrite (BNF), iron oxide (Nanomag® D-SPIO), Feridex™, and dextran-coated Johns Hopkins University (JHU) particles at a target concentration of 50pg Fe/cell using poly-D-lysine transfection reagent. T2-weighted MRI of serial dilutions of these labelled cells was performed at 9.4T and iron content quantification was performed using inductively coupled plasma mass spectrometry (ICP-MS). Clonogenic assay was used to characterise cytotoxicity. Results: No cytotoxicity was observed at twice the target intracellular iron concentration (∼100pg Fe/cell). ICP-MS revealed highest iron uptake efficiency with BNF and JHU particles, followed by Feridex and Nanomag-D-SPIO, respectively. Imaging data showed a linear correlation between increased intracellular iron concentration and decreased T2 times, with no apparent correlation among MNP magnetic properties. Conclusions: This study demonstrates that for the range of nanoparticle concentrations internalised by cancer cells the signal intensity of T2-weighted MRI correlates closely with absolute iron concentration associated with the cells. This correlation may benefit applications for cell-based cancer imaging and therapy including nanoparticle-mediated drug delivery and hyperthermia.
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U2 - 10.3109/02656736.2014.913321
DO - 10.3109/02656736.2014.913321
M3 - Article
C2 - 24773041
AN - SCOPUS:84899723473
SN - 0265-6736
VL - 30
SP - 192
EP - 200
JO - International Journal of Hyperthermia
JF - International Journal of Hyperthermia
IS - 3
ER -