Abstract
Iron oxide nanoparticles (IONPs) are suitable materials for contrast enhancement in magnetic resonance imaging (MRI). Their potential clinical applications range from diagnosis to therapy and follow-up treatments. However, a deeper understanding of the interaction between IONPs, culture media and cells is necessary for expanding the application of this technology to different types of cancer therapies. To achieve new insights of these interactions, a set of IONPs were prepared with the same inorganic core and five distinct coatings, to study their aggregation and interactions in different physiological media, as well as their cell labelling efficiency. Then, a second set of IONPs, with six different core sizes and the same coating, were used to study how the core size affects cell labelling and MRI in vitro. Here, IONPs suspended in biological media experience a partial removal of the coating and adhesion of molecules. The FBS concentration alters the labelling of all types of IONPs and hydrodynamic sizes ≥ 300 nm provide the greatest labelling using the centrifugation-mediated internalization (CMI). The best contrast for MRI results requires a core size range between 12–14 nm coated with dimercaptosuccinic acid (DMSA) producing R2* values of 393.7 s−1 and 428.3 s−1, respectively. These findings will help to bring IONPs as negative contrast agents into clinical settings.
Highlights
In vitro and in vivo nanoparticle (NP)-cell labelling, and tracking have become very promising techniques in biomedicine due to their clinical applications, spanning from regenerative medicine to the diagnosis and treatment of several diseases [1,2,3]
We found that iron oxide nanoparticles (IONPs) suspended in biological media experience a partial removal of the coating and adhesion of proteins and other molecules
The fetal bovine serum (FBS) concentration alters the centrifugation-mediated internalization (CMI)-mediated internalization of all types of IONPs assayed, except in those coated with CMD
Summary
In vitro and in vivo nanoparticle (NP)-cell labelling, and tracking have become very promising techniques in biomedicine due to their clinical applications, spanning from regenerative medicine to the diagnosis and treatment of several diseases [1,2,3]. IONPs are already used for the treatment of different tumors, mainly prostate [6] and glioblastoma [7], as well as contrast agents in magnetic resonance imaging (MRI) or magnetic particle imaging (MPI) and, in general, are considered to be relatively safe [8] Their use has been approved in humans within clinical assay context to test enhancement of MRI diagnostic for different type of cancers [9,10,11,12,13,14,15,16], Multiple Sclerosis [17,18], myocardial infarction [19,20], vascular Inflammation in migraine. Experimental results using the CMI and other classical methods, together with numerical simulations of different transport mathematical models, provided evidence that the colloidal properties of IONPs have a strong influence on their internalization by cells, and that the coating of IONPs plays an important role in this process [27]
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