330
M. Avolio et al.
treatment, indeed, relies in its potential for greater selectivity, as MFH allows extraheating, induced by the controlled application of an external alternating magnetic
field (AMF), only in the region where the heat mediators (MNPs) are localized. In
principle, MNPs are delivered near or inside the tumor cells where, depending on
the temperature reached, it is possible to cause an irreversible damage without tissue
necrosis (41–46 °C) or the complete necrosis of the tumor by thermoablation (more
than 46 °C, up to 56 °C) [19, 20]. It has been also demonstrated that, in the case
of moderate temperature increase (41–43 °C), the hyperthermia treatment enhances
the effect of conventional therapies, as chemotherapy or radiotherapy [21, 22]. The
temperature rise of the tumor cells and the consequent destroying effect is directly
related to the heating power of the MNP, i.e., its specific absorption rate (SAR)
value. In the last decades, the number of publications proposing new nanodevices
based on inorganic core with large SAR values has increased exponentially [23]. The
macroscopic temperature rise of the target tissue, however, is not the only parameter
to be considered. The capability of the nanoplatform to be internalized by the cells
[24] or to provide a “Magnetically Mediated Energy Delivery” (MagMED [25]) able
to amplify the effectiveness of the construct are additional items that must be taken
into account. For efficiently realizing a nano-device with the best performance and
multiple features, it is thus important to make it able to reach the target, by direct
injection or by chemical targeting delivery, and directly interact with the tumor cells
and sub-cellular elements. The mean to achieve this goal is the surface coating of
the MNPs, which determines their interaction with the cells and all the elements of
the physiological environment and provides multiple functionalities. The major aim
of the surface coating is indeed to protect the magnetic core from degradation while
preserving its properties over time, and at the same time, to allow overcoming the
physiological barriers, increasing the circulation time by shielding the MNP inorganic
core from the reticulo-endothelial system captures [26, 27]. The complexity of the
MNPs bio-distribution inside the body and their interaction with it at all the scales,
from organs, down to sub-cellular elements, makes very hard predicting the behavior,
and thus, in vivo effectiveness of all the proposed nanosystems. The need of a better
knowledge of MNP fate inside the body and the comprehension of the cellular uptake
mechanisms are at the base of the development of this therapeutic approach, which
represents a potential breakthrough for cancer treatment.
14.3 Physical Principles
14.3.1 Magnetic Resonance Imaging
In nuclear magnetic resonance (NMR), a radiofrequency (RF) signal is collected
from the nuclei of a given species to investigate the properties of matter. Nuclear
spins are in fact used as local probes, undergoing static homogeneous magnetic field
M. Avolio et al.
treatment, indeed, relies in its potential for greater selectivity, as MFH allows extraheating, induced by the controlled application of an external alternating magnetic
field (AMF), only in the region where the heat mediators (MNPs) are localized. In
principle, MNPs are delivered near or inside the tumor cells where, depending on
the temperature reached, it is possible to cause an irreversible damage without tissue
necrosis (41–46 °C) or the complete necrosis of the tumor by thermoablation (more
than 46 °C, up to 56 °C) [19, 20]. It has been also demonstrated that, in the case
of moderate temperature increase (41–43 °C), the hyperthermia treatment enhances
the effect of conventional therapies, as chemotherapy or radiotherapy [21, 22]. The
temperature rise of the tumor cells and the consequent destroying effect is directly
related to the heating power of the MNP, i.e., its specific absorption rate (SAR)
value. In the last decades, the number of publications proposing new nanodevices
based on inorganic core with large SAR values has increased exponentially [23]. The
macroscopic temperature rise of the target tissue, however, is not the only parameter
to be considered. The capability of the nanoplatform to be internalized by the cells
[24] or to provide a “Magnetically Mediated Energy Delivery” (MagMED [25]) able
to amplify the effectiveness of the construct are additional items that must be taken
into account. For efficiently realizing a nano-device with the best performance and
multiple features, it is thus important to make it able to reach the target, by direct
injection or by chemical targeting delivery, and directly interact with the tumor cells
and sub-cellular elements. The mean to achieve this goal is the surface coating of
the MNPs, which determines their interaction with the cells and all the elements of
the physiological environment and provides multiple functionalities. The major aim
of the surface coating is indeed to protect the magnetic core from degradation while
preserving its properties over time, and at the same time, to allow overcoming the
physiological barriers, increasing the circulation time by shielding the MNP inorganic
core from the reticulo-endothelial system captures [26, 27]. The complexity of the
MNPs bio-distribution inside the body and their interaction with it at all the scales,
from organs, down to sub-cellular elements, makes very hard predicting the behavior,
and thus, in vivo effectiveness of all the proposed nanosystems. The need of a better
knowledge of MNP fate inside the body and the comprehension of the cellular uptake
mechanisms are at the base of the development of this therapeutic approach, which
represents a potential breakthrough for cancer treatment.
14.3 Physical Principles
14.3.1 Magnetic Resonance Imaging
In nuclear magnetic resonance (NMR), a radiofrequency (RF) signal is collected
from the nuclei of a given species to investigate the properties of matter. Nuclear
spins are in fact used as local probes, undergoing static homogeneous magnetic field