Abstract
Biocompatibility has prompted a great amount of research in iron oxide nanoparticles (IONPs) as alternative magnetic resonance imaging (MRI) contrast agents. Iron concentration analysis is a key parameter to determine the relaxivities of IONPs as MRI contrast agents. Currently available methods for iron quantification are mainly inductively coupled plasma mass spectrometry (ICP-MS) and ferrozine-based iron assays. ICP spectrometry may not be easily accessible for routine analysis while iron assays are highly sensitive to sample preparation. In this paper, we present an alternative method for quantifying iron concentration using nuclear magnetic resonance (NMR) relaxometry, a technique commonly used for developing MRI contrast agents. To quantify iron concentration with NMR, a standard curve of relaxation rate versus iron concentrations was created to obtain the relaxivity of Fe3+ iron in solution. After dissolving IONPs in an acid, the iron concentration of the solution can be obtained using the relaxation times and the relaxivity of Fe3+ iron from the standard curve. The accuracy and sensitivity of this NMR method were verified by comparing with ICP analysis and ferrozine-based iron assays. Results indicate that this NMR method for iron concentration analysis was accurate for concentrations as low as 0.005 mM. In addition, the relaxivity of Fe3+ iron was sensitive to the type of acids to dissolve the IONPs, indicating that the same acid should be used for sample dissolution and the standard curve.
Highlights
Iron oxide nanoparticles (IONPs) have been extensively studied for biological applications, such as targeted drug delivery[1,2] and magnetic resonance imaging (MRI),[3,4,5] largely due to their biocompatibility[6] and magnetic properties.[7]
Iron quantification is critically important when exploring the biomedical application of IONPs, used as MRI contrast agents, in cell-based therapy, or drug delivery.[15,21,32–34]
nuclear magnetic resonance (NMR) offers an alternative method for iron quantification when using IONPs as MRI contrast agents, such as r1 and r2 relaxivity measurements
Summary
Iron oxide nanoparticles (IONPs) have been extensively studied for biological applications, such as targeted drug delivery[1,2] and magnetic resonance imaging (MRI),[3,4,5] largely due to their biocompatibility[6] and magnetic properties.[7] In particular, IONPs, as negative MRI contrast agents have been clinically approved and some are still in clinical use for iron deficiency treatment.[8] Recently, IONPs, by tuning their size and shape, have been used for positive (T1) MRI contrast effects.[9,10] For biomedical applications, knowing the iron concentration is essential because of its toxicity. NP relaxivity is the key parameter for evaluating the effectiveness of a contrast agent, for either positive (T1)[11] or negative (T2)[12] contrast enhancement or comparison across samples.[13,14]
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