Among the different materials that have been developed, inorganic NPs have
many favorable properties such as easy fabrication, tunable size, generation of heat
or reactive oxygen species (ROS), X-ray absorption, and energy transfer properties
[22]. Herein, we will provide a brief review on the types of inorganic NPs that are
being studied for radionanomedicine applications.
2.2 Magnetic Nanoparticles
Magnetic NPs (MNPs) comprises a class of extensively studied nanomaterials that
have been used in a diverse range of biomedical applications, such as imaging, drug
delivery, cancer therapy (hyperthermia) and cell labeling [23]. The advantages of
MNPs are based on their large availability and unique combination of physical and
chemical properties, including facile synthesis methods, easily-modified surface
chemistry, and magnetic responsiveness. MNPs are also advantageous due to their
established good biocompatibility in comparison to other multifunctional nanomaterials with low degradability and in vivo elimination rate [24]. Furthermore, the
ability to enhance proton relaxation of specific tissues, enable their detectability by
MRI, an imaging technique that allows acquisition of morphological and anatomical data without tissue penetration limitation [25]. Most importantly, if the ability
to respond to a magnetic field is explored, MNPs can be useful theranostics tools
[26].
Depending on the constituents of the contrast agents, magnetic NPs can be
categorized into (i) superparamagnetic iron oxide NPs (SPIONs) based T2 contrast
agents, and (ii) paramagnetic gadolinium (Gd) or manganese (Mn) based T1 contrast agents [16]. The three main categories of biologically suitable iron oxide NPs
(IONPs); magnetite (Fe 3 O 4 ), maghemite (c-Fe 2 O 3 ) and hematite (a-Fe 2 O 3 ), can
be further classified as standard superparamagnetic iron oxide (SSPIO)
(*60–150 nm) or ultra-small superparamagnetic iron oxide (USPIO; approximately 5–40 nm) NPs [27]. Size parameters not only determine their biological
behavior but are known to affect their magnetization capacity, dispersibility, and
stability in solution. To be useful for theranostic purposes, IONPs must be
monodispersed, with high magnetization, large susceptibility and small hydrodynamic size to avoid the mononuclear phagocytic system, but still large enough to
not affect its magnetic properties [28]. Since IONPs tend to agglomerate in solution,
the strategy of using coating materials such as organic polymers (PEG, chitosan,
polysorbate, polyaniline), or surfactants (sodium oleate and dodecylamine), and
others (liposomes, inorganic metals) have been successfully to date, resulting in
improved in vivo behavior [26].
Different SPION formulations are currently approved for clinical use such as the
Ferridex I.V.
® or Endorem
® for spleen and liver imaging [29], Ferumoxytol
® for
iron replacement therapy, and Combidex
® for imaging lymph node metastases [30],
as well as Gastromark
® , Resovist
® and Sinerem
® as MRI contrast agents [31]. PET/
MRI is a rising hybrid imaging technology that combines excellent soft tissue
16
C. A. Ferreira et al.
many favorable properties such as easy fabrication, tunable size, generation of heat
or reactive oxygen species (ROS), X-ray absorption, and energy transfer properties
[22]. Herein, we will provide a brief review on the types of inorganic NPs that are
being studied for radionanomedicine applications.
2.2 Magnetic Nanoparticles
Magnetic NPs (MNPs) comprises a class of extensively studied nanomaterials that
have been used in a diverse range of biomedical applications, such as imaging, drug
delivery, cancer therapy (hyperthermia) and cell labeling [23]. The advantages of
MNPs are based on their large availability and unique combination of physical and
chemical properties, including facile synthesis methods, easily-modified surface
chemistry, and magnetic responsiveness. MNPs are also advantageous due to their
established good biocompatibility in comparison to other multifunctional nanomaterials with low degradability and in vivo elimination rate [24]. Furthermore, the
ability to enhance proton relaxation of specific tissues, enable their detectability by
MRI, an imaging technique that allows acquisition of morphological and anatomical data without tissue penetration limitation [25]. Most importantly, if the ability
to respond to a magnetic field is explored, MNPs can be useful theranostics tools
[26].
Depending on the constituents of the contrast agents, magnetic NPs can be
categorized into (i) superparamagnetic iron oxide NPs (SPIONs) based T2 contrast
agents, and (ii) paramagnetic gadolinium (Gd) or manganese (Mn) based T1 contrast agents [16]. The three main categories of biologically suitable iron oxide NPs
(IONPs); magnetite (Fe 3 O 4 ), maghemite (c-Fe 2 O 3 ) and hematite (a-Fe 2 O 3 ), can
be further classified as standard superparamagnetic iron oxide (SSPIO)
(*60–150 nm) or ultra-small superparamagnetic iron oxide (USPIO; approximately 5–40 nm) NPs [27]. Size parameters not only determine their biological
behavior but are known to affect their magnetization capacity, dispersibility, and
stability in solution. To be useful for theranostic purposes, IONPs must be
monodispersed, with high magnetization, large susceptibility and small hydrodynamic size to avoid the mononuclear phagocytic system, but still large enough to
not affect its magnetic properties [28]. Since IONPs tend to agglomerate in solution,
the strategy of using coating materials such as organic polymers (PEG, chitosan,
polysorbate, polyaniline), or surfactants (sodium oleate and dodecylamine), and
others (liposomes, inorganic metals) have been successfully to date, resulting in
improved in vivo behavior [26].
Different SPION formulations are currently approved for clinical use such as the
Ferridex I.V.
® or Endorem
® for spleen and liver imaging [29], Ferumoxytol
® for
iron replacement therapy, and Combidex
® for imaging lymph node metastases [30],
as well as Gastromark
® , Resovist
® and Sinerem
® as MRI contrast agents [31]. PET/
MRI is a rising hybrid imaging technology that combines excellent soft tissue
16
C. A. Ferreira et al.