Magnetic Nanoparticles as MRI Contrast Agents

Abstract

Iron oxide nanoparticles (IONPs) have emerged as a promising alternative to conventional contrast agents (CAs) for magnetic resonance imaging (MRI). They have been extensively investigated as CAs due to their high biocompatibility and excellent magnetic properties. Furthermore, the ease of functionalization of their surfaces with different types of ligands (antibodies, peptides, sugars, etc.) opens up the possibility of carrying out molecular MRI. Thus, IONPs functionalized with epithelial growth factor receptor antibodies, short peptides, like RGD, or aptamers, among others, have been proposed for the diagnosis of various types of cancer, including breast, stomach, colon, kidney, liver or brain cancer. In addition to cancer diagnosis, different types of IONPs have been developed for other applications, such as the detection of brain inflammation or the early diagnosis of thrombosis. This review addresses key aspects in the development of IONPs for MRI applications, namely, synthesis of the inorganic core, functionalization processes to make IONPs biocompatible and also to target them to specific tissues or cells, and finally in vivo studies in animal models, with special emphasis on tumor models.

Keywords: Cancer; Diagnosis; Iron oxide nanoparticles; Magnetic nanoparticles; Magnetic resonance imaging.

Fig. 1

Methods used in the synthesis of iron oxide nanoparticles (IONPs)

Fig. 2

LaMer’s model depicting the nucleation and growth process of the nanoparticles. Adapted with permission from [10]. Copyright (1950) American Chemical Society

Fig. 3

Different stages during the synthesis of IONPs in the thermal decomposition method. Adapted and modified with permission from [41]. Copyright (2013) American Chemical Society

Fig. 4

Synthesis of chitosan derivative polymeric micelles encapsulating superparamagnetic iron oxide nanoparticles (SPIONs) [308]

Fig. 5

Schematic illustration of alginate/polyethilenimine-iron (III) oxide (AG/PEI-Fe₃O₄) and stem-cell-mediated delivery of nanogels (NGs) for enhanced breast or glioma tumor molecular resonance (MR) imaging. Reprinted with permission from [241]. Copyright (2019) Royal Society of Chemistry

Fig. 6

Synthesis of mesoporous silica-coated (ms)-IONPs. Polyvinylpyrrolidone (PVP)-10 was added to IONPs prior to cetyltrimethylammonium bromide (CTAB) addition and silica condensation to allow for CTAB colocalization with IONPs and to maintain a spacer layer between the silica shell and IONP core. Reprinted with permission from [245]. Copyright (2016) American Chemical Society

Fig. 7

C6 brain tumor model implanted orthotopically (upper panels) and heterotopically (lower panels). Left) T₂-weighted MR images before the injection of IONPs; right) T₂-weighted MR images 1 h after the injection of IONPs

Fig. 8

Scheme of the non-targeted (top) and targeted IONPs (bottom)

Fig. 9

a In vivo MR images of a NCr nude mouse at different time points after intravenous injection of IONPs. b Quantification of liver contrast collected at different time points after accumulation of IONPs in NCr nude mice. c In vivo MR images of liver tumor orthotopic xenographs at different time points after intravenous injection of IONPs. d Quantification of contrast-to-noise ratio (CNR) of tumor-to-liver contrast at different time points. e, f Histopathological analysis of mouse liver 1 h after the intravenous injection of IONPs. Reprinted with permission from [292]. Copyright (2018) American Chemical Society