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Figure from:Magnetic nanoparticles for medical applications: Progress and challenges

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Conventional radiotherapy treatments emit beams capable of penetrating tissues, allowing for their application in treating tumors located deep in the body. However, the main complication is the lack of selectivity between tumor cells and healthy cells, imiting the application of these treatments. Future challenges for the development of radiotherapies include targeting radiation doses only to cancerous tissue while enhancing beneficial biological properties. Nanotechnology has provided a crucial advance in cancer treatment. The addition of NPs of elements with high atomic numbers (Z), for example, Pt (Z = 78) and Au (Z = 79), has been shown to reduce radiation damage to healthy issues in vitro and in vivo [120,121] and increase the yield of free radicals in the area. The probable mechanisms could be explained by a photoelectric effect, releasing X-rays, and short-range Auger-type electron beams, which have an energy lower than 5 keV, energy sufficient to damage DNA and ionize water molecules in medium (Figure 8) [122] and thus expanding the interactions with lower-energy photons at higher atomic numbers [123,124]. The combination of radiotherapy-NPs is an innovative proposal to improve selectivity towards cancer tissue and treatment procedures through an adequate coating of NPs, increasing their circulation time and active direction. Figure 8. Schematic depiction of increased generation of reactive species by the emission of photo- electrons and Auger electrons from AuNPs in the presence of ionizing radiation.

Figure 8 Conventional radiotherapy treatments emit beams capable of penetrating tissues, allowing for their application in treating tumors located deep in the body. However, the main complication is the lack of selectivity between tumor cells and healthy cells, imiting the application of these treatments. Future challenges for the development of radiotherapies include targeting radiation doses only to cancerous tissue while enhancing beneficial biological properties. Nanotechnology has provided a crucial advance in cancer treatment. The addition of NPs of elements with high atomic numbers (Z), for example, Pt (Z = 78) and Au (Z = 79), has been shown to reduce radiation damage to healthy issues in vitro and in vivo [120,121] and increase the yield of free radicals in the area. The probable mechanisms could be explained by a photoelectric effect, releasing X-rays, and short-range Auger-type electron beams, which have an energy lower than 5 keV, energy sufficient to damage DNA and ionize water molecules in medium (Figure 8) [122] and thus expanding the interactions with lower-energy photons at higher atomic numbers [123,124]. The combination of radiotherapy-NPs is an innovative proposal to improve selectivity towards cancer tissue and treatment procedures through an adequate coating of NPs, increasing their circulation time and active direction. Figure 8. Schematic depiction of increased generation of reactive species by the emission of photo- electrons and Auger electrons from AuNPs in the presence of ionizing radiation.

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Table 1. Coatings of NPs with possible medical applications. 3. Magnetic Drug-Delivery System (MDDS)
Table 1. Coatings of NPs with possible medical applications. 3. Magnetic Drug-Delivery System (MDDS)
Figure 2. Pathway for a drug to reach a diseased part using MDDS plays a fundamental role since it distributes the MNPs throughout the body and then concentrates them using a magnetic field, as shown in Figure 2 [77]. Therefore, MNPs must meet a specific size to reach diseased tissue because they must pass through the pulmonary capillaries and avoid phagocytosis. It is recommended that the MNPs have a size of less than 100 nm to achieve this goal, reducing pain in the surrounding tissue when concentrated. However, if the MNPs are too small, they will not be able to show the proper magnetic behavior to be directed adequately with an external magnetic field [78]. Ideally, MNPs should present a high magnetization at body temperature, and once the magnetic field is removed, they should not retain the magnetization, avoiding the formation of aggregates capable of forming emboli and facilitating their elimination from the body.
Figure 2. Pathway for a drug to reach a diseased part using MDDS plays a fundamental role since it distributes the MNPs throughout the body and then concentrates them using a magnetic field, as shown in Figure 2 [77]. Therefore, MNPs must meet a specific size to reach diseased tissue because they must pass through the pulmonary capillaries and avoid phagocytosis. It is recommended that the MNPs have a size of less than 100 nm to achieve this goal, reducing pain in the surrounding tissue when concentrated. However, if the MNPs are too small, they will not be able to show the proper magnetic behavior to be directed adequately with an external magnetic field [78]. Ideally, MNPs should present a high magnetization at body temperature, and once the magnetic field is removed, they should not retain the magnetization, avoiding the formation of aggregates capable of forming emboli and facilitating their elimination from the body.
Likewise, a C¢o-based solid could produce a strong magnetic field at low temperatures, 17 T at 29 K [87]; similarly, Gd-Ba-Cu-O, 3 T at 77 K [86]. For example, SmBaCuO and YBaCuO-type HTS were used as external magnetic field sources to drive 100 nm MNPs through a Y-shaped glass tube with blood flow. The results indicated a 90% accumulation of the NPs due to the magnetic force of the superconducting magnet at 20 mm (Figure 3). These experimental results indicate that MNPs can target and accumulate in a controlled manner, even at a flow rate of 100 mms~! [88]. Figure 3. Schematic representation of an MDDS operated under the influence of external magnetic field.
Likewise, a C¢o-based solid could produce a strong magnetic field at low temperatures, 17 T at 29 K [87]; similarly, Gd-Ba-Cu-O, 3 T at 77 K [86]. For example, SmBaCuO and YBaCuO-type HTS were used as external magnetic field sources to drive 100 nm MNPs through a Y-shaped glass tube with blood flow. The results indicated a 90% accumulation of the NPs due to the magnetic force of the superconducting magnet at 20 mm (Figure 3). These experimental results indicate that MNPs can target and accumulate in a controlled manner, even at a flow rate of 100 mms~! [88]. Figure 3. Schematic representation of an MDDS operated under the influence of external magnetic field.
Figure 4. Evolution of the magnetic energy with the tilt angle between the easy axes
Figure 4. Evolution of the magnetic energy with the tilt angle between the easy axes
Figure 5. Néel relaxation is the rotation of magnetic moment inside a stationary MNP. Brownian relaxation is the rotation of entire MNP along with the magnetic moment. Various research studies on the mechanism of heat generation have shown that the size of MNPs strongly affects the rate of heating [98]. Furthermore, due to the Brownian and Néel relaxation, time constants are modified depending on the particle. However, the SAR is the main parameter to determine the tissue heating rate. In general, the SAR is expressed in units of watts per kilogram (W/kg) and is proportional to the rate of temperature rise (AT/At) for the adiabatic case, as shown by the following equation (Equation (1)):
Figure 5. Néel relaxation is the rotation of magnetic moment inside a stationary MNP. Brownian relaxation is the rotation of entire MNP along with the magnetic moment. Various research studies on the mechanism of heat generation have shown that the size of MNPs strongly affects the rate of heating [98]. Furthermore, due to the Brownian and Néel relaxation, time constants are modified depending on the particle. However, the SAR is the main parameter to determine the tissue heating rate. In general, the SAR is expressed in units of watts per kilogram (W/kg) and is proportional to the rate of temperature rise (AT/At) for the adiabatic case, as shown by the following equation (Equation (1)):
Figure 6. Scheme of therapeutic strategy using MNPs. Functionalized MNPs accumulate in the tumot tissue, then start with the hyperthermia treatment.
Figure 6. Scheme of therapeutic strategy using MNPs. Functionalized MNPs accumulate in the tumot tissue, then start with the hyperthermia treatment.
Figure 7. Schematic illustration of MNPs functionalized with clorotoxin and Cy5.5.
Figure 7. Schematic illustration of MNPs functionalized with clorotoxin and Cy5.5.