Topics in Current Chemistry (2020) 378:40
1 3
1 Introduction
Magnetic resonance imaging (MRI) is one of the main in vivo imaging modalities,
along with positron emission tomography (PET), computed tomography (CT) and
ultrasound imaging. MRI is the most versatile of all of these, being able to provide
both anatomical and functional information with excellent image quality, and, most
importantly, using non-ionizing radiation, which allows longitudinal studies to be
performed without the risk of side effects. The MRI signal comes from the radiofrequency signal of protons magnetized by an external magnetic field. These protons
originate mainly from water molecules. The application of radiofrequency pulses is
used to excite the magnetization, and magnetic field gradients are used to provide
spatial localization. Contrast in MRI reflects differences in signal intensity, which
depends on the concentration of water molecules within the tissue, the relaxation
times, T 1 and T 2 , of the water protons and the mobility of the water molecules (diffusion, flow) [1]. Additionally, image contrast can be further enhanced using contrast agents (CAs), with Gd-chelates being used most commonly in clinical practice. However, CAs lack specificity and have recently been related to toxicity issues
caused by the unexpected release of free Gd. Magnetic nanoparticles have emerged
as a promising alterative with improved properties in terms of specificity and biocompatibility. Over the past two decades, many studies have aimed at the development of new magnetic nanomaterials that can serve to improve the diagnosis and
treatment of many different diseases. Among these nanomaterials, iron oxide nanoparticles (IONPs) have been investigated most extensively as CAs for MRI due to
their magnetic properties, that is, the superparamagnetism that leads to very high
relaxivity, their high biocompatibility, since they can be incorporated into iron
metabolism, and also the easy functionalization of their surfaces with target molecules for molecular imaging purposes [2].
The first step in the development of IONPs is synthesis of the magnetic core,
for which many different methods have been proposed, all aiming at strict control of the size, shape and magnetic properties, so that the synthesis process can
be performed under highly reproducible conditions, which is one of the essential
requirements for the potential clinical translation of these new nanomaterials [3].
Functionalization of magnetic nanoparticles is then needed to make them soluble
in aqueous media and to provide them with stability and biocompatibility [4].
Further functionalization may include the addition of different molecules to target
specific tissues or cells [5]. The most relevant functionalization strategies will be
discussed in detail in this review. Finally, the in vivo characterization of IONPs
is the most critical aspect in the development of IONPs for biomedical applications. Although many new nanomaterials show excellent in vitro properties, most
of them fail when tested in vivo. Thus, around 6500 studies (PubMed database)
on magnetic nanoparticles have been published since 2010, in which IONPs
often appear as promising new CAs for MRI. However, up to now, extremely low
clinical translation has been achieved [6]. Therefore, comprehensive studies with
appropriate in vivo experimental models are of paramount importance for the
successful development and eventual clinical translation of these nanomaterials.
50
Reprinted from the journal
1 3
1 Introduction
Magnetic resonance imaging (MRI) is one of the main in vivo imaging modalities,
along with positron emission tomography (PET), computed tomography (CT) and
ultrasound imaging. MRI is the most versatile of all of these, being able to provide
both anatomical and functional information with excellent image quality, and, most
importantly, using non-ionizing radiation, which allows longitudinal studies to be
performed without the risk of side effects. The MRI signal comes from the radiofrequency signal of protons magnetized by an external magnetic field. These protons
originate mainly from water molecules. The application of radiofrequency pulses is
used to excite the magnetization, and magnetic field gradients are used to provide
spatial localization. Contrast in MRI reflects differences in signal intensity, which
depends on the concentration of water molecules within the tissue, the relaxation
times, T 1 and T 2 , of the water protons and the mobility of the water molecules (diffusion, flow) [1]. Additionally, image contrast can be further enhanced using contrast agents (CAs), with Gd-chelates being used most commonly in clinical practice. However, CAs lack specificity and have recently been related to toxicity issues
caused by the unexpected release of free Gd. Magnetic nanoparticles have emerged
as a promising alterative with improved properties in terms of specificity and biocompatibility. Over the past two decades, many studies have aimed at the development of new magnetic nanomaterials that can serve to improve the diagnosis and
treatment of many different diseases. Among these nanomaterials, iron oxide nanoparticles (IONPs) have been investigated most extensively as CAs for MRI due to
their magnetic properties, that is, the superparamagnetism that leads to very high
relaxivity, their high biocompatibility, since they can be incorporated into iron
metabolism, and also the easy functionalization of their surfaces with target molecules for molecular imaging purposes [2].
The first step in the development of IONPs is synthesis of the magnetic core,
for which many different methods have been proposed, all aiming at strict control of the size, shape and magnetic properties, so that the synthesis process can
be performed under highly reproducible conditions, which is one of the essential
requirements for the potential clinical translation of these new nanomaterials [3].
Functionalization of magnetic nanoparticles is then needed to make them soluble
in aqueous media and to provide them with stability and biocompatibility [4].
Further functionalization may include the addition of different molecules to target
specific tissues or cells [5]. The most relevant functionalization strategies will be
discussed in detail in this review. Finally, the in vivo characterization of IONPs
is the most critical aspect in the development of IONPs for biomedical applications. Although many new nanomaterials show excellent in vitro properties, most
of them fail when tested in vivo. Thus, around 6500 studies (PubMed database)
on magnetic nanoparticles have been published since 2010, in which IONPs
often appear as promising new CAs for MRI. However, up to now, extremely low
clinical translation has been achieved [6]. Therefore, comprehensive studies with
appropriate in vivo experimental models are of paramount importance for the
successful development and eventual clinical translation of these nanomaterials.
50
Reprinted from the journal