Magnetic Nanoparticles in Human Health and Medicine. Группа авторов

W g_Fe⁻¹). This finding can be explained by the lack of hysteresis losses contribution, the existence of large anisotropic fields, and the formation of 3D aggregates. The same trend was observed by Nemati et al. (2018). In their study, the SAR dropped from 800 to 300 W g_Fe⁻¹ as the size of FeMIONs nanocubes was increased from 30 to 106 nm. The coating of large FeMIONs nanocubes with gallol‐polyethylene glycol prevents their aggregation in big clusters and hence increases their SAR value up to 1400 W g_Fe⁻¹ (H × f = 7.7 × 10⁹ A m⁻¹ s⁻¹). A very high SAR (2614 W g_Fe⁻¹, H × f = 0.66 × 10⁹ A m⁻¹ s⁻¹) has been reported for FeMIONs nanocubes of 30 nm in size coated with chitosan, probably as a consequence of the hysteresis losses contribution (Bae et al. 2012). Local symmetry breaking as a result of structural defects, broken symmetry bonds, and surface strain causes the deformation of the nanocubes into nanooctopods (Nemati et al. 2016). Similar to cubic MNPs, the enhanced shape anisotropy of the nanooctopods with size ranging from 17 to 47 nm led to an increase in the heating efficiency from 285 to 415 W g_Fe⁻¹ (H × f = 20 × 10⁹ A m⁻¹ s⁻¹) with respect to spherical MNPs.

      Octahedral SPIONs presented also enhanced SAR values compared to the spherical MNPs owing to their higher Ms (Mohapatra et al. 2015; Lv et al. 2015). It was found that octahedrons with size between 6 and 12 nm exhibited SAR values between 163 and 275 W g_Fe⁻¹ (H × f = 6.1 × 10⁹ A m⁻¹ s⁻¹) (Mohapatra et al. 2015). The hysteresis losses generated by the octahedral FeMIONs with size between 40 and 98 nm have boosted the SAR values in the 2480–2630 W g_Fe⁻¹ range (H × f = 23 × 10⁹ A m⁻¹ s⁻¹) (Lv et al. 2015). In this category, one has to mention the polyhedral FeMIONs with a mean size of 34 nm, who displayed a saturation SAR value around 1900 W g_Fe⁻¹ (H × f = 14.2 × 10⁹ A m⁻¹ s⁻¹) (Iacovita et al. 2016).

In the last years, elongated IOMNPs with tunable aspect ratio, the so‐called “nanorods,” received a particular attention (Geng et al. 2016; Das et al. 2016). The pronounced unidirectional shape anisotropy of nanorods having an aspect ratio of 11 (65 nm length × 5.7 nm width) led to an increase in the saturation magnetization and effective anisotropy that improved their heating efficiency up to 862 W g_Fe⁻¹ (H × f = 20 × 10⁹ A m⁻¹ s⁻¹). For comparison, their cubic and spherical counterparts of similar magnetic volumes presented much lower values (314 W g_Fe⁻¹ for cubes and 140 W g_Fe⁻¹ for spheres) (Das et al. 2016). Moreover, the rapid alignment of nanorods, parallel with the external applied AMF, increases appreciably the SAR values up to 1300 W g_Fe⁻¹ (Das et al. 2016). Nanorods with an aspect ratio of 4.5 (45 nm length × 10 nm width), synthesized by the reduction of akaganeite (β‐FeOOH) in organic solvents, exhibited SAR value up to 1072 W g_Fe⁻¹ (H × f = 13 × 10⁹ A m⁻¹ s⁻¹) (Carrey et al. 2011). Instead, nanorods with a larger aspect ratio (10 : 400 nm length × 40 nm width) displayed low SAR value at the same AMF parameters probably due to a higher switching field necessary to reverse their magnetization (Geng et al. 2016).

      Among the different classes of iron oxide MNPs presented so far, vortex iron oxide MNPs (VIONs) present outstanding magnetic hyperthermia response, when compared to standard SPIONs, while preserving low cytotoxicity. The VIONs explore a peculiar magnetic configuration known as a magnetic vortex, in which the iron magnetic moment curls in concentric circles, confining the magnetic flux within MNPs. Hence, the VIONs have no magnetic pole and a negligible remanent magnetization, avoiding thus the aggregation due to dipolar interaction. It has been shown that nanorings with an average outer diameter of 70 nm, heights of 50 nm, and an inner to outer diameter ratio of ~0.6, displayed a saturation SAR value of 3050 W g_Fe⁻¹ (H × f = 23.6 × 10⁹ A m⁻¹ s⁻¹) (Liu et al. 2015), while the SAR value of hexagonal nanodiscs with 225 nm in diameter and 26 nm in thickness can be increased up to 4400 W g_Fe⁻¹ by increasing the AMF to 47.8 kA m⁻¹ (H × f = 23.3 × 10⁹ A m⁻¹ s⁻¹) (Yang et al. 2015b). The parallel alignment of both types of VIONs with AMF and the hysteresis losses induced by the vortex domain structure contribute to the high SAR values observed for these morphologies. Nanodiscs with smaller dimensions (12 nm in diameter and 3 nm in thickness) exhibit a very low SAR value (125 W g_Fe⁻¹) despite the high H × f factor used (20 × 10⁹ A m⁻¹ s⁻¹). This is due to the lack of vortex domain configuration (Nemati et al. 2017). For H × f factors below the imposed limit, nanodiscs (150–200 nm in diameter and 10–15 nm in thickness), nanorings (average outer diameter of 165 nm, heights of 75 nm, and an inner to outer diameter ratio of ~0.4), elongated nanorings (average outer diameter of 155 nm, heights of 170 nm, and an inner to outer diameter ratio of ~1), and nanotubes (average outer diameter of 130 nm, heights of 250 nm, and an inner to outer diameter ratio of ~0.45) displayed SAR values of 245 W g_Fe⁻¹ (Ma et al. 2013), 426, 368 and 401 W g_Fe⁻¹, respectively (Dias et al. 2017).

2.3 Conclusions and Final Remarks

      MNPs exhibit different magnetism from their bulk counterparts, and this particularity makes them ideal candidates for several biomedical applications. Their first application approved for clinical practice was CAs in MRI, but over the time, the advancement in the field of synthesis methods, multiplied their bioapplications. Based on their capacity to accumulate in malign tumors, the most common application of MNPs as MRI CAs is for early detection and diagnosis of cancer.

      But MNPs can be used for monitoring cell therapies by cell tracking. Large numbers of MNPs can be loaded into cells by electroporation, magnetofection or cell‐penetrating peptides and single cell detection can be achieved in vitro. Moreover, recent studies showed that the MNPs accumulate in lysosomes without affecting the cell functions. The combined use of MNPs and MRI provided information in different pathological processes such as atherosclerosis, pancreatic islet inflammation, or cardiac allograft rejection.

      On the other hand, different nanohybrid formulations based on MNPs able to operate as dual T₁ − T₂ contrast agents have been reported. This finding demonstrates the huge potential of these nanostructures in MRI applications.

Very recently, the MNPs have been employed in cell tracking applications using MPI and MPS. By using different classes of MNPs displaying a specific magnetic response, it became possible to study in vivo the interactions between the cells and the MNPs they are loaded with, opening new perspectives in applications related to nanomedicine.

      Nevertheless, the MNPs have been extensively tested in therapeutical applications based on MH, and the results are encouraging. During this chapter, we tried to present the most important classes of iron oxide MNPs that can be used for such applications. Given the current strict regulation, we believe that iron oxides MNPs will remain the first choice in the case of MNPs‐based MH. We truly believe that by carefully controlling their characteristics, multifunctional nanohybrids based on MNPs will be able to fulfill all the requirements necessary for their successful use in clinical practice.

Acknowledgments

      This research was funded by the Romanian National Authority for Scientific Research, CNCSIS‐UEFISCDI, through the research project for exploratory research No. PN‐III‐P4‐ID‐PCCF‐2016‐0112 and demonstration experimental project PN‐III‐P2‐2.1‐PED‐2019‐3283.

References

      1 Alphandéry, E., Faure, S., Raison, L. et al. (2011). Heat production by bacterial magnetosomes exposed to an oscillating magnetic field. The Journal of Physical Chemistry C 115 (1): 18–22.

      2 Arruebo,