14 Medical Applications of Magnetic Nanoparticles
339
the body: SPIOs are sequestered by the Kupffer cells in the reticuloendothelial
system, primarily in the liver, while USPIOs circulate longer into the blood before
being captured by macrophages (monocytes) and to accumulate in liver and spleen
[62, 63]. Particularly, the blood pool half-life of USPIOs in humans is more than
24 h [64], while for SPIOs it has been estimated to be shorter than 6 min [65]. More
generally, the cellular uptake by monocytes increases with the particle size [59]; in
this regard, Engberink et al. [59] reported a significant hypointense signal (increased
r 2 ) coming from human monocytes labelled with 150 nm SPIOs compared to cells
incubated with 30 nm USPIOs, proving a size-dependent uptake.
On the other hand, a high heating power, or SAR value, of the inorganic magnetic
component of the nanodevice is the first requirement to assure its effectiveness for
therapeutic application by MFH. In principle, this can be achieved by choosing a
material with enhanced magnetic properties in its bulk phase and tuning them at the
nanoscale as exemplified in Fig. 14.3. In fact, while the magnetization saturation and
the magnetic anisotropy are intrinsic properties of the chosen material, its size and
the size dispersion can be accurately tuned to fit the frequency of the external field
[see (14.7)]. Based on this simple concept, many MNPs with different composition
and morphological structure have been proposed as heat mediators for MFH. Unfortunately, most of those reporting huge SAR values are made of pure metal or metallic
alloys, including potentially toxic elements, like cobalt [66, 67], which, due to their
high concentration and weak chemical stability, have poor chance of being approved
by the competent authorities in Europe and USA for use in medicine. Since the beginning, when MFH was proposed by Gilchrist in 1957 [68], iron oxide nanoparticles
have been suggested as appropriate candidates for heat mediators because of their
biological compatibility as the iron accidentally released can be recycled through the
metabolic pathways. Also in this case the most commonly proposed materials are
spinel ferrite magnetite (Fe 3 O4) and maghemite (γ-Fe 2 O 3 ) thanks to their superior
magnetic properties, which, adopting simple, accurate synthetic procedures, can be
maintained at the nanoscale size [69]. Nanoparticles of excellent crystallinity and
chemical purity can be routinely obtained in the range of sizes established by the
theory and confirmed by the experiments for optimizing the hyperthermic efficacy
(12–20 nm for magnetite [70], and 15–25 nm for maghemite [71, 72]). In this class of
materials, improvements have been done by using mixed ferrites (M x Fe 3−x O 4 where
M is a divalent metallic cation), containing low percentage of other metals to not
compromise the natural biocompatibility of the compound. Following this strategy,
notable results have been recently reported for maghemite MNPs weakly-doped by
magnesium ions [73]. Highly controlled synthetic procedure allowed preparation of
monodispersed (δ < 10%) MNPs of Mg 0.13 -γFe 2 O 3 of 7 nm average size with giant
(>10 kW/g) SAR value (Fig. 14.5). We stress that this result was obtained by applying
an AFM within the tolerance limit (partial body exposure) and that the Mg-doping
assures a good biocompatibility. It should be remarked, indeed, that, even though the
tolerance limit condition needs a better definition, many of the highest SAR values
reported in the literature [74] were obtained using field parameters well outside any
theoretical or empirical constrains, making the translation to clinics trails unfeasible.
339
the body: SPIOs are sequestered by the Kupffer cells in the reticuloendothelial
system, primarily in the liver, while USPIOs circulate longer into the blood before
being captured by macrophages (monocytes) and to accumulate in liver and spleen
[62, 63]. Particularly, the blood pool half-life of USPIOs in humans is more than
24 h [64], while for SPIOs it has been estimated to be shorter than 6 min [65]. More
generally, the cellular uptake by monocytes increases with the particle size [59]; in
this regard, Engberink et al. [59] reported a significant hypointense signal (increased
r 2 ) coming from human monocytes labelled with 150 nm SPIOs compared to cells
incubated with 30 nm USPIOs, proving a size-dependent uptake.
On the other hand, a high heating power, or SAR value, of the inorganic magnetic
component of the nanodevice is the first requirement to assure its effectiveness for
therapeutic application by MFH. In principle, this can be achieved by choosing a
material with enhanced magnetic properties in its bulk phase and tuning them at the
nanoscale as exemplified in Fig. 14.3. In fact, while the magnetization saturation and
the magnetic anisotropy are intrinsic properties of the chosen material, its size and
the size dispersion can be accurately tuned to fit the frequency of the external field
[see (14.7)]. Based on this simple concept, many MNPs with different composition
and morphological structure have been proposed as heat mediators for MFH. Unfortunately, most of those reporting huge SAR values are made of pure metal or metallic
alloys, including potentially toxic elements, like cobalt [66, 67], which, due to their
high concentration and weak chemical stability, have poor chance of being approved
by the competent authorities in Europe and USA for use in medicine. Since the beginning, when MFH was proposed by Gilchrist in 1957 [68], iron oxide nanoparticles
have been suggested as appropriate candidates for heat mediators because of their
biological compatibility as the iron accidentally released can be recycled through the
metabolic pathways. Also in this case the most commonly proposed materials are
spinel ferrite magnetite (Fe 3 O4) and maghemite (γ-Fe 2 O 3 ) thanks to their superior
magnetic properties, which, adopting simple, accurate synthetic procedures, can be
maintained at the nanoscale size [69]. Nanoparticles of excellent crystallinity and
chemical purity can be routinely obtained in the range of sizes established by the
theory and confirmed by the experiments for optimizing the hyperthermic efficacy
(12–20 nm for magnetite [70], and 15–25 nm for maghemite [71, 72]). In this class of
materials, improvements have been done by using mixed ferrites (M x Fe 3−x O 4 where
M is a divalent metallic cation), containing low percentage of other metals to not
compromise the natural biocompatibility of the compound. Following this strategy,
notable results have been recently reported for maghemite MNPs weakly-doped by
magnesium ions [73]. Highly controlled synthetic procedure allowed preparation of
monodispersed (δ < 10%) MNPs of Mg 0.13 -γFe 2 O 3 of 7 nm average size with giant
(>10 kW/g) SAR value (Fig. 14.5). We stress that this result was obtained by applying
an AFM within the tolerance limit (partial body exposure) and that the Mg-doping
assures a good biocompatibility. It should be remarked, indeed, that, even though the
tolerance limit condition needs a better definition, many of the highest SAR values
reported in the literature [74] were obtained using field parameters well outside any
theoretical or empirical constrains, making the translation to clinics trails unfeasible.