Magnetic Nanoparticles in Human Health and Medicine. Группа авторов

As shown by Gazeau et al., the size selection of SPIONs with 30 nm in diameter increases their heating performance to 600 W g_Fe⁻¹, at clinically relevant conditions (H × f = 4.1 × 10⁹ A m⁻¹ s⁻¹) (Gazeau et al. 2008).

      An alternative approach for increasing SPIONs heating rates turned out to be the control of their surface coating. It has been shown that dextran‐coated SPIONs with a diameter of 7 nm display a SAR value of 626 W gFe⁻¹ (H × f = 6.25 × 10⁹ A m⁻¹ s⁻¹) (Mornet et al. 2004). Liu et al. reported a maximum SAR value of 930 W g_Fe⁻¹ (H × f = 10.8×10⁹ A m⁻¹ s⁻¹) when SPIONs with a diameter of 19 nm are coated with a 6 nm shell of phosphorylated methoxy polyethylene glycol 2000 (Liu et al. 2012). Interestingly, the high heating capacity of PEGylated SPIONs is maintained in various physiological conditions. On the other hand, the inorganic coating can also improve the SAR value of SPIONs. For example, Mohammad et al. found that the hyperthermic effect of SPIONs is four‐ to fivefold enhanced (920 W g_Fe⁻¹) on coating with a gold shell of 0.5 thickness (Mohammad et al. 2010). A maximum SAR value of 1300 W g_Fe⁻¹ (H × f = 7.9×10⁹ A m⁻¹ s⁻¹) was measured for dumbbell‐like shaped dimers formed by an iron oxide domain of 24 nm in size and a gold seed of 9 nm in diameter (Guardia et al. 2017).

When the SPIONs size exceeds the SP limit, the thermal energy cannot overcome anymore the barrier of magneto‐crystalline anisotropy, and the MNPs acquire a permanent magnetic dipole moment, pointing in the direction of the easy axis. The MNPs become ferromagnetic at room temperature, developing hysteresis loops, which are characterized by M_r and coercivity (H_c – magnetic field strength required for demagnetization). The MH properties of ferromagnetic IOMNPs (FeMIONs) are now dictated by their dynamic hysteresis behavior (Carrey et al. 2011). The synergistic contribution from the hysteresis and susceptibility (Neel and Brown) loss enhance the SAR values of FeMIONs in comparison with SPIONs. Several research teams have obtained the following maximum SAR values for FeMIONs of different diameters synthesized via thermal decomposition of magnetic precursors in organic solvent: 650 W g_Fe⁻¹ (H × f = 19.1 × 10⁹ A m⁻¹ s⁻¹) for 52 nm FeMIONs (Nemati et al. 2018); 716 W g_Fe⁻¹ (H × f = 7.75 × 10⁹ A m⁻¹ s⁻¹) for 22 nm FeMIONs (Chen et al. 2013); 801 W g_Fe⁻¹ (H × f = 13.2 × 10⁹ A m⁻¹ s⁻¹) for 28 nm FeMIONs (Mohapatra et al. 2018) and 2560 W g_Fe⁻¹ (H × f = 6.7 × 10⁹ A m⁻¹ s⁻¹) for 40 nm FeMIONs (Tong et al. 2017). The increase of FeMIONs sizes can be realized up to a certain threshold value; above it, the FeMIONs might enter into a multimagnetic domains state that will lead to a decrease in their SAR values (Chen et al. 2013; Mohapatra et al. 2018; Nemati et al. 2018). Despite the large amounts of generated heat, FeMIONs are less favorable for biomedical applications due to their colloidal instability and Hc that facilitate their aggregation. The dipole–dipole interactions manifested between FeMIONs significantly influence their heating efficiency (Serantes et al. 2010; Salas et al. 2014; Coral et al. 2016). But when these interactions, coupled with the uniaxial shape anisotropy, will arrange (Toulemon et al. 2016) or align (Jiang et al. 2016) the FeMIONPs into chain‐like superstructures, their Hc and Ms will increase. Consequently, the heating performances will be enhanced as it was shown theoretically (Serantes et al. 2014) and experimentally (Myrovali et al. 2016). Through polyol‐mediated synthesis, the stabilization of the FeMIONs may occur as multicore aggregates: nanoclusters (Sakellari et al. 2016), hollow nanospheres (Gavilán et al. 2017), and nanoflowers (Hugounenq et al. 2012; Gavilán et al. 2017). Due to the collective spin rotation, the SAR value of these aggregates is much greater than of their constituents. For instance, nanoflowers of 50 nm consisting of spherical FeMIONs of 11 nm displayed SAR values of 1790 W g_Fe⁻¹ (H × f = 7.7 × 10⁹ A m⁻¹ s⁻¹) (Hugounenq et al. 2012), while nanoflowers of 60 nm consisting of spherical FeMIONs of 22 nm presented SAR values of 1180 W g_Fe⁻¹ (H × f = 17 × 10⁹ A m⁻¹ s⁻¹) (Gavilán et al. 2017).

A particular class of iron oxide MNPs that hold great potential for MH applications are the magnetosomes, produced by magnetostatic bacteria. Unlike chemically synthesized iron oxide MNPs, the magnetosomes are directly synthesized in chain‐like structures consisting of perfectly stoichiometric nanocrystals with controlled sizes and shapes, surrounded by a biocompatible membrane. These characteristics reduce magnetosomes' cellular toxicity. At the same time, they are able to deliver large amounts of heat (Prabhu 2016; Cypriano et al. 2019). For instance, two studies reported SAR values of 880 W g_Fe⁻¹ (H × f = 5 × 10⁹ A m⁻¹ s⁻¹) (Muela et al. 2016) and 960 W g_Fe⁻¹ (H × f = 4 × 10⁹ A m⁻¹ s⁻¹) (Hergt et al. 2005) for magnetosomes produced by the same bacteria: Magnetospirillum gryphiswaldense. As shown by Alphandery et al., chains of magnetosomes inside Magnetospirillum magneticum strain AMB‐1 bacteria yielded a SAR value of 864 W g_Fe⁻¹ (H × f = 7.6 × 10⁹ A m⁻¹ s⁻¹) (Alphandéry et al. 2011). It was enhanced up to 1242 W g_Fe⁻¹, upon the extraction of magnetosomes chains from bacteria, potentially due to the Brownian friction within the liquid. The removal of the membrane surrounding the magnetosomes followed by the disruption of the chains resulted in a decrease of the SAR value down to 950 W g_Fe⁻¹. The highest SAR values reported so far were obtained for magnetosomes inside M. gryphiswaldense bacteria dispersed in water: 2400 W g_Fe⁻¹ (H × f = 9 × 10⁹ A m⁻¹ s⁻¹) (Gandia et al. 2019). The heating efficiency of the magnetosomes was reduced by half (~1200 W g_Fe⁻¹), when the bacteria were randomly distributed in 2% agar medium. When bacteria were aligned parallel to the AFM, the SAR values almost returned to its initial value (2100 W g_Fe⁻¹). This could be a strong evidence of the fact that in water, the bacteria align parallel with the AFM. In this case, the Brownian relaxation of the magnetosomal chains played a minor role being embedded in bacterial matrix. As a consequence, their mutual magnetic interactions are strongly reduced. When these bacteria have been internalized in human lung carcinoma cells A549, the cellular viability and growth were not affected. But the MH experiments, performed on these cells, strongly affected the cancer cell proliferation, making these bacteria promising candidates for cancer applications. Spherical IOMNPs exhibit multiple facets featuring many edges and corners. This type of curved morphology displays many disordered surface spins. The large surface canting effects and high‐surface anisotropy strongly affect the heat dissipation properties of spherical IOMNPs (Noh et al. 2017).

      As it was pointed out before, the second strategy for heat generation improvement consisted in tuning the effective anisotropy of IOMNPs by modifying their shape. It has been theoretically demonstrated that cubic MNPs have lower surface anisotropy compared to spheres due to a smaller amount of disordered spins (4 vs. 8%). Several experimental studies have confirmed this phenomenon. The comparison between cubic and spherical IOMNPs, with similar magnetic volumes, show an important increase of SAR values in the case of cubic IOMNPs: 356.2 vs. 189.6 W g_Fe⁻¹ (H × f = 6 × 10⁹ A m⁻¹ s⁻¹) (Bauer et al. 2016); 314 vs. 140 W g_Fe⁻¹ (H × f = 20 × 10⁹ A m⁻¹ s⁻¹) (Das et al. 2016); 395 vs. 150 W g_Fe⁻¹ (H × f = 19.1 × 10⁹ A m⁻¹ s⁻¹) (Nemati et al. 2018) and 1963 vs. 410 W g⁻¹ (H × f = 6.6 × 10⁹ A m⁻¹ s⁻¹) (Elsayed et al. 2017). An extensive research on the heating properties of cubic IOMNPs with sizes ranging from 13 to 38 nm has been performed by Guardia et al. under different conditions of field and frequency (Guardia et al. 2012, 2014). They found that the nanocubes with a mean size of 19 nm exhibit SAR value as high as 2453 W g_Fe⁻¹ (H × f =