Assessing heating efficiencies of PVPylated divalent metal-doped MFe2O4 nanoparticles for magnetic hyperthermia

Assessing heating efficiencies of PVPylated divalent metal-doped MFe2O4 nanoparticles for magnetic hyperthermia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Assessing heating efficiencies of PVPylated divalent metal-doped MFe2O4 nanoparticles for magnetic hyperthermia Kheireddine El-Boubbou, O. Mohamed Lemine, Saja Algessair, Nawal Madkhali, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3872967/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract There is an incessant demand to keep improving on the heating responses of polymeric magnetic nanoparticles (MNPs) under magnetic excitation, particularly in their pursuit to be utilized for clinical hyperthermia applications. Herein, we report the fabrication of a panel of PVP-coated metal-doped MFe 2 O 4 (M ≅ Co, Ni, Mn, Zn) MNPs prepared via the Ko-precipitation Hydrolytic Basic (KHB) methodology and assess their magnetic and self-heating abilities. The physiochemical, structural, morphological, compositional, and magnetic properties of the doped MNPs were fully characterized using various spectroscopic techniques mainly TEM, XRD, FTIR, and VSM. The obtained MNPs exhibited stabilized quasi-spherical sized particles (10–15 nm), well-crystallized cubic inverse spinel phases, high saturation magnetizations (26–81 emu/g) and ferromagnetic behavior. In response to alternating magnetic field (AMF), distinctive heating responses of these doped ferrite NPs were attained. Heating efficacies and specific absorption rate (SAR) values as functions of concentration, frequency, and amplitude were systematically investigated. The highest heating performance was observed for PVP-NiFe 2 O 4 followed by PVP-CoFe 2 O 4 and the least for PVP-Zn-doped and Mn-doped MNPs (SAR values Ni > Co > Zn > Mn). Finally, cytotoxicity assay was conducted on aqueous dispersions of the doped ferrite NPs, proving their biocompatibility and low toxicity. Our results strongly suggest that the PVPylated metal-doped ferrite NPs prepared here, particularly Ni- and Co-doped MNPs, are promising vehicles for potential combined magnetically-triggered biomedical hyperthermia applications. Physical sciences/Chemistry Physical sciences/Chemistry/Materials chemistry Physical sciences/Nanoscience and technology Physical sciences/Nanoscience and technology/Nanoscale materials Physical sciences/Materials science Physical sciences/Materials science/Nanoscale materials Magnetic hyperthermia iron oxide nanoparticles magnetite doped iron oxides doped ferrites SAR ILP Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 1. Introduction Magnetic iron oxide nanoparticles (MNPs) have been widely used for biomedical applications in magneto-responsive biomedical applications including biosensing, drug delivery, magnetic resonance imaging (MRI), and magnetic fluid hyperthermia (MFH) 1–4 . Particularly, in magnetic hyperthermia an implanted magnetic material is utilized under an external alternating magnetic field (AMF) to dissipate heat from MNPs in the area of concern 5 . This approach has become one of the promising potential treatments for cancer as it enables to destroy malignant solid tumors by ablation (T = 45–46 ◦ C) or mild heating (T = 40–45 ◦ C) with minimal side effects. MNPs with their metal (iron (Fe), cobalt (Co), or nickel (Ni) etc.) oxide compartments have been successfully used in this regard 6,7 . They own ferromagnetic and superparamagnetic properties that make them align with the applied magnetic field and, hence, release energy as heat, cooking and killing the target cells selectively. Among the various MNPs, magnetite (Fe 3 O 4 ) is the most commonly studied material for cancer hyperthermia treatment due to its low toxicity, ease of synthesis, and FDA approval 8,9 . It is clearly evident, from our and other reports 10–13 , that the heating efficiencies of MNPs are affected by several parameters such as size and shape of the NPs, saturation magnetization (M s ), magnetic anisotropy constant, NP concentration, surface modification as well as the amplitudes and frequency of the applied magnetic field under various experimental conditions. In order to keep improving on the heat dissipated by MNPs, typically computed by specific absorption rate (SAR) and intrinsic loss power (ILP) values, one approach often consists of tuning the magnetic properties of these MNPs by doping the construct with divalent transition metals to prepare ferrite NPs 14–17 . Metal Ferrites MFe 2 O 4 (M = Co, Ni, Zn, Mn) are well-studied for magnetic hyperthermia applications, though, with limited outcome 15,18–21 . The unique ferrite structural stability properties allow more controllable physiochemical properties. This is due to the ability of atom transition between the tetrahedral and octahedral sites within the crystal, which causes alteration in magnetic properties 22 . Moreover, applying different divalent transition metals within the ferrite structure produces distinct magneto-thermal properties depending on their atomic specification (ionic radius and ionic strength) and the amount of ions doped. Hence, different ferrite structures own unique properties such as grain and crystallite sizes as well as different ranges of saturation magnetization, which in turn affects the heating efficiencies 23 . For instance, previous studies have confirmed that Co-ferrite (CoFe 2 O 4 ) NPs have a higher saturation magnetization and exhibit greater magnetic properties than magnetite (Fe 3 O 4 ) due to the presence of Co 2+ ions in the octahedral sites 24 . Moreover, very good heating abilities of various sizes and shapes of Ni-ferrite NPs were reported 25 26 , with the possibility of tuning the SAR values by changing experimental settings. Zinc ferrites were also applied successfully either alone or mixed with Co or Ni in limelight to find their use as heat mediators in magnetic hyperthermia 27–29 . Moreover, MnFe 2 O 4 NPs were also explored as candidates for hyperthermia with reasonably good SAR values 30 . Nonetheless, without proper coating, the usage of such materials is impractical for biomedical applications due to their high toxicity and sensitivity to oxidation. It is of immense importance that ferrite NPs are incorporated with polymers to enhance their biocompatibility and stability in physiological media, lower their toxicities, minimize their agglomeration and solution precipitation, and boost their controlled heat dissipation 27,31 . It has been also shown that surface functionalization and polymer coating can enhance the heating efficiencies of the MNPs, in cases where the combination of polymers and metals results in enhanced heat transmission 32–34 . Metals with excellent thermal conductivity, such as iron oxide NPs, enable efficient heat generation when subjected to an external AMF. The polymer matrix functions as a thermal insulator, preventing excessive heat dissipation and concentrating the generated heat in the target tissue 33,35–37 . This controlled and localized heating allows for more accurate treatment while reducing damage to neighboring healthy tissues and increasing hyperthermia's therapeutic efficiency 34 . Furthermore, the use of polymer coating the metal cores enables multifunctionality in hyperthermia applications, where polymers can be made to have a variety of features, including biodegradability, biocompatibility, and drug-loading. Thus, for clinical hyperthermia applications, preparation of polymer-coated doped magnetic NPs, MFe 2 O 4 (where M ≅ Co, Mn, Ni, or Zn) and decoding their specific magneto-thermal heating capabilities are highly demanded. Herein, a panel of PVP-coated metal-doped MFe 2 O 4 (where M ≅ Co, Mn, Ni, Zn) NPs was prepared using our Ko-precipitation Hydrolytic Basic (KHB) methodology to be utilized for magnetic hyperthermia. We evaluated and studied the magnetic and thermal responses of the various as-prepared PVPylated metal-doped magnetic NPs. We then investigated, systematically, the effects of concentration, field amplitude, and frequency on SAR values for the obtained doped MNPs under safe clinical magnetic field conditions. PVP was chosen as it is widely used in the pharmaceutical industry as a non-ionic water-soluble polymer as dispersant, binder, and suspender. Moreover, we have shown in our previous work the superior heating power of PVP-coated Fe 3 O 4 NPs over other employed polymeric magnetite NPs (i.e. PEG, Dextran, HA, and PAA). To the best of our knowledge, this is the first report systematically studying the heating efficiencies of various PVPylated doped MFe 2 O 4 NPs for hyperthermia applications. 2. Experimental Section 2.1. Materials and Methods. All chemicals and solvents were obtained from commercial suppliers and used as supplied without further purification. Iron(III) chloride hexahydrate (FeCl 3 .6H 2 O), iron(II) sulfate heptahydrate (FeSO 4 .7H 2 O), Cobalt(II) chloride hexahydrate (CoCl 2 .6H 2 O), Nickel(II) chloride hexahydrate (NiCl 2 .6H 2 O), Zinc chloride hexahydrate (ZnCl 2 .6H 2 O), Stannous chloride hexahydrate (SnCl 2 .6H 2 O), Manganese chloride hexahydrate (MnCl 2 .6H 2 O), Copper(II) chloride hexahydrate (CuCl 2 .6H 2 O), Polyvinylpyrrolidone (PVP Mw ~ 27,000 ), and 28% ammonium hydroxide (NH 4 OH) were all purchased from Sigma Aldrich. All reactions were carried out under inert nitrogen atmosphere. For biological assays, Dulbecco’s Phosphate Buffered Saline (DPBS), Phosphate Buffered Saline (PBS), Advanced Dulbecco's Modified Eagle Medium (DMEM), Phenol-red free DMEM, Fetal Bovine Serum (FBS), Hoechst 33342 stain, L-Glutamine, and Penicillin-Streptomycin (Pen-Strep) were all purchased from Invitrogen. MTT (Thiazolyl Blue Tetrazolium Bromide) powder was purchased from Bioworld, USA. All cell lines were purchased from the American Type Culture Collection (ATCC) and grown in Advanced DMEM supplemented with 10% FBS and 1% Penicillin/Streptomycin. Human cancerous cells used in this study are: MDA-MB-231 (metastatic breast cancer cell line) and KAIMRC1 (naturally immortalized KAIMRC1 breast cancer cells isolated from a 62-year-old Arab female suffering from stage IIB breast cancer). All experiments were conducted in triplicates and mean. Characterization X-ray diffraction (XRD) using Rigaku Uitima IV equipped with Cu-Kα radiation source (0.15418 nm) with angle ranging from 10⁰ to 80⁰ and the crystal structure parameters were obtained through Rietveld analysis. The morphology of the samples was studied by means of transmission electron microscope (TEM). TEM micrographs of the MNPs were obtained using a Titan 300 kV ST (FEI) electron microscope. Prior to TEM imaging, we treated the TEM grids with plasma to remove organics and dust. For TEM imaging, a few drops of the doped MFe 2 O 4 samples were drop-casted on the TEM grids and dried under vacuum. Compositional and chemical analysis were performed on the samples using core-loss electron energy loss spectroscopy (EELS) in nanoscale. Fourier transform infrared (FTIR) spectra (400–4000 cm-1) were recorded as KBr pellet forms using Shimadzu IRAffinity-1. Magnetic characterizations were performed using vibrating sample magnetometer (VSM) with 1.8 T magnets at ambient temperature. 2.2. Preparation of PVP-coated MFe 2 O 4 NPs by KHB method. All MNPs were prepared using our previously reported KHB method as illustrated in Fig. 1 . FeCl 3 .6H 2 O (0.30 g) was mixed with PVP (0.2 g) dissolved in water (10 mL) and stirred for few minutes at 80 °C under nitrogen. FeSO 4 .7H 2 O: MCl 2 .6H 2 O (0.1 g: 0.1 g) dissolved in water was then injected into the above solution. Ammonium hydroxide NH 4 OH 28 % (~ 3 mL) was slowly added where the solution turned black-brick colored depicting the formation of doped MNPs. Stirring was continued for 24 hrs to allow better crystalline phases. The NP suspensions were then purified via centrifugation (4500 rpm, 5 min), washed several times with isopropanol, ethanol, and water, and finally re-dispersed in water to afford stable aqueous dispersions of PVP-coated doped MFe 2 O 4 NPs. For the preparation of Fe3O4 MNPs, same procedure was followed using 0.2 g of Fe 2+ precursor. 2.3. Evaluation of Heating Efficiencies . The heating efficiency of the samples was performed using a commercial system "Nanotherics Magnetherm" as reported in our previous works 13,18,33 . Different concentrations (10, 7.5, 5, and 2.5 mg/mL) of doped MNPs have been investigated at 170 Oe and 332.8 kHz for the field amplitude and frequency, respectively. The samples were dissolved in distilled water and sonicated for 10 min and the temperature increase of the samples was then recorded for 15 min. 2.4. Cell Viability Assay . Cell viability of breast cancer MDA-MB231 and KAIMRC1 cells exposed to different concentration of MNPs was determined using MTT assay. The cell lines were seeded in a 96-well plate at a density of 5 × 10 5 cells/ well and incubated in 95%/5% humidified air/CO 2 at 37 °C. After overnight incubation, cells were treated with various concentrations of control and metal-doped samples in 100 μL of supplemented DMEM. After 48 h of incubation, the medium was removed, and the cells were washed with PBS. Then, 5 μL of MTT reagent (5 mg/mL) was added to each well and kept for 4 h at 37 °C in the incubator. The supernatant was then removed, and 100ul of dimethyl sulfoxide (DMSO) was added to each well. The absorbance was measured on the Molecular Devices Spectrophotometer absorbance reader at 590 nm. The percentage of viable cells was calculated as the ratio of the absorbance of the treated group divided by the absorbance of the control group multiplied by 100. 3. Results and Discussion 3.1. Preparation and characterization of MFe 2 O 4 MNPs. All MNPs were prepared using our previously reported KHB method as illustrated in Fig. 1 . Briefly, sequential in situ basic hydrolytic precipitation of iron salts (Fe 3+ and M 2+ : Fe 2+ ; 1:1) in the presence of PVP afforded stable aqueous dispersions of PVP-coated metal-doped MFe 2 O 4 -MNPs. The obtained doped MNPs were characterized by various electronic and spectroscopic techniques including TEM, XRD, and VSM. These techniques clearly revealed the structure, morphology, and magnetization of the as-synthesized MFe 2 O 4 NPs. TEM images (Fig. 2 a) clearly indicated the quasi-spherical morphology of all ferrite NPs, with average sizes of 10 nm except for Ni ferrite NPs (sizes ~ 17 nm) as depicted by their corresponding particle size-distribution (Fig. 2 b). High-resolution TEM (HR-TEM) indicates that the NPs show close-packed 2D array of relatively uniform sized particles clearly showing the interfringe lattices of the NPs. Each particle is a well-ordered single crystal despite their small size. In fact, the distance between two adjacent lattice fringes obtained by HR-TEM analysis of a single nanocrystal is calculated to be ~ 0.25 nm corresponding to the lattice spacing of (311) planes of magnetite 38 . To elucidate the crystalline structure and identify which phase we have, XRD was performed. XRD patterns of all MFe 2 O 4 samples are illustrated in Fig. 3 a, showing well-crystallized inverse spinel structures. Well-defined peaks are observed for each spectrum indicating the crystalline nature of the samples. For all samples, main peaks were defined at (220), (311), (400), (422), (511), (440), and (533) which are related to the spinel structure. Both Co and Ni ferrite possess a fully inverse structure due to the chemical nature of Ni 2+ and Co 2+ which tend to occupy octahedral sites while Fe 3+ occupy tetrahedral ones 39 . Rietveld analysis of these XRD spectra confirmed the formation of pure MFe 2 O 4 cubic spinel phases with space group Fd3m for NiFe 2 O 4, CoFe 2 O 4 , ZnFe 2 O 4 , and MnFe 2 O 4 which matches well with JCPDS # 01-071-3850, # 01-074-6402, # 01-071-5149, and # 01-071-4919, respectively. The refinements show an excellent agreement between the observed and calculated patterns (Fig. 3 b). No additional peaks have been observed suggesting that the synthetic method leads to the formation of a pure spinel ferrite phase. From Rietveld analysis of XRD results, the crystallite size, microstrain, and lattice parameters of all samples were calculated as shown in Table 1 . Different sizes of crystals were formed depending on the metal ferrite ranging from 5.2 nm for MnFe 2 O 4 to 18.5 nm for NiFe 2 O 4 . Such variation in crystallite size between different metal ferrites might be due to the difference in the ionic radii of the dopant metals 40 . The lattice parameters also varied but slightly from 1.13 to 0.09. The unit cell of the MFe 2 O 4 ferrite structures deduced from Rietveld shows that iron ions are tetrahedrally and octahedrally coordinated to oxygens, where doping with M 2+ did not alter much either the crystal structure or the lattice parameter (Fig. 4 a). This is expected as the substitution of Fe 3+ ions by very small amounts of M 2+ ions ((Fe 3+ : M 2+ ; 3: 1) would not induce geometrical distortion in the unit cell 18 . Regarding SnFe 2 O 4 sample, the XRD spectra indicated less crystallinity as the peaks were not sharp. The Rietveld analysis showed its best match with the orthogonal Sn 0.096 Fe 1.874 O 3 phase. TEM-EDS elemental analysis was then performed to further confirm the purity of the as-synthesized doped samples. For instance, the presence of Fe, O, C, and Co peaks for Co-doped ferrite NPs without any additional element reveal the high purity of the obtained ferrites. The spatial distribution of each component within the NPs was investigated using the STEM-EDS spectrum imaging (SI) method, 41 and the obtained elemental mappings of the elements are shown in Fig. 4 b,c. The uniform distribution was observed in the generated map of each element. Each sample's black and white image represents the High Angle Annular Dark Field (HAADF) imaging, while the red, green, cyan, and blue colors represent Fe, O, C, and Co elements, respectively. The lower brightness of the C element explains the decrease of its atomic percentage compared to Fe, Co, or O. Table 1 Rietveld analysis results of XRD spectra of PVPylated MFe 2 O 4 NPs. Sample (Phase %) DB card No. Size (nm) Micro strain Lattice Parameter (A ◦ ) Fitting Parameters PVP-Fe 3 O 4 01-071-6337 9 0.314 (7) a:8.344 Rwp: 41.4 Rp: 31.06 Re: 37.85 (100%) b:8.344 c:8.344 S: 1.09 X2 1.19 PVP-NiFe 2 O 4 01-071-3850 18.52 0.093 (6) a:8.355 Rwp: 38.58 Rp: 27.38 Re: 36.92 (100%) b:8.355 c:8.355 S: 1.0441 X2 1.09 PVP-CoFe 2 O 4 9.3 0.09 (7) a:8.379 Rwp: 41.29 Rp: 30.42 Re: 41.61 (100%) 01-074-6402 b:8.379 c:8.379 S: 0.9915 X2 0.983 PVP-ZnFe 2 O 4 01-071-5149 8.9 0.343 (12) a:8.436 Rwp: 24.11 Rp: 16.76 Re: 22.91 (100%) b:8.436 c:8.436 S: 1.05 X2 1.1 PVP-MnFe 2 O 4 01-071-4919 5.2 1.13 (4) a:8.355 Rwp: 29.68 Rp: 22.84 Re: 27.24 (100%) b:8.355 c:8.355 S: 1.08 X2 1.18 PVP-Sn 0.09 6Fe 1.874 O 3 01-088-0432 2.5 0.58 (6) a:5.093 Rwp: 28.22 Rp: 22.87 Re: 19.66 b:5.093 c:13.93 S: 1.43 X2 2.05 Next, FTIR analysis was conducted to further validate the successful formation of PVP-coated MFe 2 O 4 NPs (Fig. 5 ). The presence of iron oxide (Fe 3 O 4 ) in the core was clearly evident by the Fe − O stretching bands at 560 and 620 cm − 1 , which appeared as one broad peak ~ 560–600 cm − 1 for the MFe 2 O 4 because of metal doping the crystallites. The distinctive peaks at 2850 and 2920 cm − 1 clearly depict the symmetric and asymmetric C-H stretching modes of PVP coating, while the broad peak at ~ 3400 cm − 1 is ascribed to the O − H stretching vibration of hydroxyl groups on MNPs. Another major signature peak is the stretching vibration of C = O carbonyl evident at ~ 1635 cm − 1 . The carbonyl of free PVP polymer typically appears at 1660 cm − 1 42,43 . This shift from 1660 cm − 1 to 1635 cm − 1 confirms the functionalization of MNPs with PVP via intermolecular hydrogen bonding between the carbonyl group of PVP and the protonated hydroxyl groups on MNP surfaces. Moreover, PVP is well-known to adsorb on the ferrite nanocrystals via coordinative bonds between the pyrrolidone molecules and the metal ions, where the donated lone pairs of both nitrogen and oxygen atoms form complex with Fe 3+ ions 44 . All these results clearly indicate the successful coating of MFe 2 O 4 ferrite NPs with PVP. 3.2. Magnetic Properties To determine the magnetic behavior of the MNPs, field-dependent magnetizations were conducted. The coating and doping can both have dominant effects on magnetization and, hence, the heating efficiencies of MNPs. Figure 6 a depicted the hysteresis loop (M–H) of the as-synthesized MNPs at 300 K, while saturation (M r ), coercivity (H c ), and remanence (M r ) values deduced from the loops are summarized in Table 2 . It can be observed that all ferrite NPs behave as soft ferromagnetic with small but non-negligible coercivity and remanence (Fig. 6 b). The saturation magnetization ( M s ) obtained for the PVP-NiFe 2 O 4 , PVP-CoFe 2 O 4 NPs, PVP-ZnFe 2 O 4 , PVP-MnFe 2 O 4 , and PVP-SnFe 2 O 4 ferrite NPs were found to be equal to 80.74, 66.17, 38.78, 26.26, 4.26 emu/g respectively. As evident the highest saturation magnetizations were found for Ni and Co-doped samples with the lowest obtained for Sn-doped iron oxide sample. This huge difference between saturation can be caused by several factors such as the type of spinel ferrites in which the synthesized samples are crystallized, the magnetic nature of the divalent cations (i.e. Co 2+ , Ni 2+ , Zn 2+ , Mn + 2 , and Sn 2+ ), their distribution in the octahedral and tetrahedral sites, size of NPs obtained, and the presence of magnetic dead layers due to the coating of the ferrite NPs by PVP. Co and Ni are ferromagnetic and interaction between Co or Ni ions spin and the lattice favors the alignment of their spins parallel to the cube edge of the spinel lattice. In addition, both ions induce uniaxial magnetic anisotropy in the magnetization direction which will increase saturation. Other divalent cations are non-magnetic where the insertion of these ions in the octahedral sites will affect Fe-ions interactions and induce decrease in long range magnetic ordering, which explained the low saturation. Importantly, the PVP-coated MFe 2 O 4 ferrite NPs obtained here have relatively high saturation magnetizations, which are larger than similar polymer-coated ferrite MNPs reported in the literature 44–47 , indicating high degree of magnetic ordering and crystallinity. For instance, Oulhakem et al. reported saturation of 18.43, 13.53, and 0.69 emu/g for alginate-encapsulated Alg@CoFe 2 O 4 , Alg@NiFe 2 O 4 , and Alg@ZnFe 2 O 4 respectively 28 . Interestingly, most studies reported decrease of saturation after coating of NPs by organic polymer/matrix 28,48 , while coating with PVP tends to increase the saturation of ferrite NPs (i.e. 80.74 emu/g for PVP-NiFe 2 O 4 ) and magnetite NPs 33 . Table 2 Magnetic parameters deduced from M-H curves and law of approach saturation. Experimental Law of saturation (LAS) Sample H c (Oe) M r (emu) M s (emu/g) M r /M s M s (emu/g) K eff (erg/cm 3 ) PVP-Fe 3 O 4 26 1.38 39.70 0.03 39.46 4.5857 PVP-NiFe 2 O 4 13 1.92 80.74 0.02 80.79 12.182 PVP-CoFe 2 O 4 218 9.60 66.17 0.14 68.35 2.75×10 5 PVP-ZnFe 2 O 4 18 0.54 38.78 0.01 39.22 3.1038 PVP-MnFe 2 O 4 16.64 0.50 26.26 0.02 25.97 3.0767 PVP-SnFe 2 O 4 54.62 0.34 4.26 0.08 4.24 0.50361 In addition to the saturation magnetization, there are three magnetic parameters, which affect the heating ability for hyperthermia application, namely: coercivity (H c ), remanence (M r ) and magnetic anisotropy constant (K eff ). The coercivity is affected by the nature of the magnetic nature of the divalent cations and reached the highest value of 218 Oe for PVP-CoFe 2 O 4 NPs. Regarding the remanence, the ratio (M r /M s ) values are in the range 0.01–0.14 which deviates largely from the value of 0.5 suggested by Stoner-Wolfahrt’s model 49 , for an ensemble of non-interacting single domain magnetic particles distributed randomly. The deviation from the theoretical value M r /M s = 0.5 could be attributed to the effect of dipolar interactions which reduces the remanence. Finally, the effective anisotropy constant (K eff ) was deduced from the fitting of the experimental magnetization as shown in Fig. 6 c by using the following Eq. 5 0 : $$\text{M}\left(\text{H}\right)={\text{M}}_{\text{s}}\left(1-\frac{\text{b}}{{\text{H}}^{2}}\right) \left(1\right)$$ where b is a parameter which is deduced from the fitting of experimental magnetization with Eq. (1). K eff is then determined by Eq. (2) as follows 51 : $${\text{K}}_{\text{e}\text{f}\text{f}}={{{\mu }}_{0}\text{M}}_{\text{s}}\sqrt{\frac{15\text{b}}{4}} \left(2\right)$$ The calculated values of K eff are summarized in the Table 2 . It can be observed that the highest value (2.75×10 5 erg/cm 3 ) is obtained for PVP-CoFe 2 O 4 NPs which shows the highest coercivity (218 Oe). It can be also noticed that saturation deduced from the fit is slightly different from the experimental values indicating the accuracy of the fitting by LAS (Fig. 6 d). 3.3. Magnetic Hyperthermia Measurements The heating performance of MNPs is intimately entwined with their structure, size, and magnetic anisotropy. For magnetic hyperthermia, the main challenges lie in obtaining NPs of specific characteristics: high heating efficiencies with minimal concentrations under clinically safe field exposure. When a magnetic system is subjected to AMF, heat is generated due to certain loss mechanisms, which can be classified as hysteresis and relaxation losses. It was specifically found that SAR values for superparamagnetic/ferromagnetic NPs (almost negligible hysteresis losses) are directly affected by parameters which influence the magnetic moment rotation responsible for heat dissipated through Brownian and Néel relaxation mechanisms 51–53 . Frequency and field amplitude of AMF also have direct effects on the heating efficiencies of the MNPs. For clinical hyperthermia applications and to satisfy medical safety conditions, there are two limitations for the product of the amplitude (H) and the frequency ( f ) for the applied magnetic field known as the Atkinson − Brezovich limit (H× f ≤ 4.85 × 108 A.m − 1 .s − 1 ) and the Hergt’s limit (H× f ≤ 5×10 9 A.m − 1 .s − 1 ) 54,55 . Thus, for an efficient clinical utilization of MNPs in hyperthermia, the heat dissipation should be optimized by using minimal dosage of polymer-coated MNPs (to ensure biocompatibility) and high magnetic properties (to guarantee efficient heating) in relatively short times. Therefore, designing tailored doped ferrite NPs that can dissipate heat at low concentrations under different ranges of frequencies and magnetic field is key to achieve a controllable and efficient hyperthermia treatments. Moreover, preparing stabilized well-dispersed magnetic NPs with high heating efficiencies and SAR values in large quantities in an easy, robust, cheap, and reproducible process is likewise demanded. The heating efficiencies of PVPylated undoped and doped ferrite NPs dispersed in water under alternating magnetic field (AMF) were evaluated. Figure 7 shows the temperature rise of aqueous dispersions of various doped ferrite NPs at different concentrations under AMF with frequency and amplitude of 332.8 kHz and 170 Oe, respectively. The main parameters that assess self-heating abilities of MNPs obtained from the temperature rise are summarized in Table 3 . As can be observed from Fig. 7 , MNPs show high heating abilities and reach magnetic hyperthermia temperatures (42°C) in relatively short times. Within 15 min, the solution with the highest concentration (10 mg/mL) reached, noticeably, higher temperatures, in comparison with 7.5, 5, and 2.5 mg/mL solutions. This dependence of the temperature rise on the concentration of NPs is expected because more heat generators (i.e. NPs) are present in the concentrated sample. The temperatures for all the samples slowly increased but did not reach saturation within the 15 min period. During the magnetic hyperthermia treatment, the temperature should be regulated at 42°C for at least 30 min to kill the malignant tumor, but it should be also kept below 46°C to prevent normal tissues from burning. Thus, all the tested doped ferrite samples (7.5 and 10 mg/mL) satisfy these conditions, particularly the PVPylated Ni- and Co-Fe 2 O 4 NPs. Interestingly, even for lower concentrations of 2.5 mg/ml, Ni-doped sample indicated a very good temperature rise and reached hyperthermia temperatures. Table 3. Heating parameters for the different doped PVP-MFe 2 O 4 NPs at various concentrations (H = 170 Oe, f = 332.8 kHz). ILP (nHm 2 /kg) (2-15 sec) SAR (W/g) (2-15 sec) Time needed to reach 42 ⁰C (min) Maximum temperature (⁰C) Concentration (mg/mL) Sample 0.498 30.253 5.57 53.97 10 PVP-Fe 3 O 4 0.353 21.456 9.73 47.42 7.5 0.456 27.679 Not reaching 40.85 5 0.487 29.610 Not reaching 34.37 2.5 0.503 30.575 11.15 48.53 10 PVP-CoFe 2 O 4 0.396 24.031 11.99 45.31 7.5 0.372 22.759 13.35 43.18 5 0.330 20.897 Not reaching 38.93 2.5 0.900 54.714 5.20 55.50 10 PVP-NiFe 2 O 4 0.840 51.066 5.73 54.66 7.5 0.636 38.622 8.93 48.85 5 0.593 36.047 11.85 44.09 2.5 0.387 23.495 10.07 45.99 10 PVP-ZnFe 2 O 4 0.257 17.165 13.07 43.55 7.5 0.413 25.104 14.41 42.20 5 0.283 19.909 Not reaching 35.00 2.5 0.339 20.598 8.58 45.50 10 PVP-MnFe 2 O 4 0.354 19.161 11.12 4 0.18 7.5 0.230 14.311 Not reaching 38.92 5 0.208 12.185 Not reaching 35.16 2.5 0.302 18.345 12.35 43.98 10 PVP-SnFe 2 O 4 0.212 12.874 Not reaching 38.90 7.5 0.116 7.0810 Not reaching 35.47 5 0.187 9.610 Not reaching 33.76 2.5 SAR values, defined as the dissipation heat generated by a unit mass of MNPs, were then determined by Eq. (3) as follows: $$SAR=\frac{{\rho C}_{w}}{{Mass}_{MNP}}\left(\frac{{\Delta }T}{{\Delta }t}\right)\left(3\right)$$ where C w is defined as the specific heat capacity of water (4.185 J/g.k), the density of the colloid is \(\rho\) , the concentration of MNPs in the suspension is called \({Mass}_{MNP}\) and the heating rate is represented by \(\frac{{\Delta }T}{{\Delta }t}\) . By performing a linear fit of temperature increase vs time at the initial time interval (1 to 30 s), the slope \(\Delta T/\Delta t\) is obtained. The calculated SAR values are summarized in Table 3 . The relatively high values indicate the good heating capabilities of the prepared ferrite NPs. There is a significant increase of SAR for PVP-NiFe 2 O 4 NPs (~ 55 W/g) compared to other samples, which is relatively higher than that of other similar reported doped magnetic NPs. It can be noted also from the table, that SAR decreases with decreasing concentration of MNPs. This is in agreement with our previous work, 33 where the dependence of the temperature rise on the concentration is expected as more heat generators are present in the concentrated samples. In addition, important parameters such as the core sizes, viscosity of the medium, and polydispersity of the samples can considerably affect SAR. Such behavior could be directly attributed to enhancement in the interparticle dipolar interactions, which influences Néel-Brownian relaxation 56 . Comparison of SAR values at 10 mg/mL concentration (Fig. 8 a), shows that PVP-NiFe 2 O 4 NPs have the highest value (54.71W/g), while PVP-SnFe 2 O 4 NPs indicate the lowest value (18.34 W/g). Difference in SAR values can be explained by the effect of many parameters as indicated above but saturation anisotropy remains the main parameter which directly affects the heating ability. Figure 8 b shows that there is direct correlation between SAR and M s values, where MNPs with the highest magnetic saturation (PVP-NiFe 2 O 4 NPs) resulted in the highest SAR, while the one with lowest saturation is recorded for PVP-SnFe 2 O 4 NPs. Thus, it can be clearly concluded that there are optimal parameters that should be produced (size, magnetization, polydispersity, coating, concentration etc) to maximize SAR values for MNPs. Finally, the effects of both the field amplitude and the frequency on self-heating ability of PVP-NiFe 2 O 4 NPs (10 mg/mL) was then investigated. Different combinations of magnetic fields and frequencies were applied. In Fig. 9 a, the frequency was fixed at 332 kHz and the magnetic field varied to 130, 150 and 170 Oe. It can be seen that the temperature rise increases with increasing field amplitude. Magnetic hyperthermia temperature (42°C) is not reached at 130 Oe, however increasing the magnetic field to 170 Oe caused a clear rise in temperature allowing the reach of 42°C. SAR values were increased with increasing field amplitude (Fig. 9 b). Similar behavior is observed when the frequency was adjusted to 113, 170 and 332 kHz, while the field was fixed to 120 Oe as shown in Fig. 9 c,d. Overall, for all applied frequencies, the maximum temperature reached by the NPs is increasing with field amplitude, leading to higher SAR values. As shown previously in Eq. 3, the calculation of SAR values depends on the initial slope of temperature rise. We can conclude that applying different combinations of frequencies and magnetic allows the tuning of self-heating characteristics of the MNPs. Finally, the intrinsic loss power (ILP), used to compare the heating efficiencies of different MNPs were calculated by using the obtained values of SAR and applying the following equation: $$ILP=SAR/fH_{0}^{2}$$ 4 where f is the frequency and H 0 is the coercivity The ILP values for different concentrations of doped MNPs under the different sets of experimental conditions and various concentrations are summarized in Table 3 . As can be observed, these values are comparable to that reported for maghemite [ 4 , 10 ], magnetite [ 21 ] and commercials ferrofluids [ 22 ]. All these results indicated that the heat dissipated by MNPs can be tuned easily by changing the concentration, field amplitude, and frequency of the AMF as reported by many other systems [ 4 , 5 , 8 , 10 ]. Such tuning depends mainly on the magnetic properties, particle size, crystallinity, interparticle interactions, dispersing medium, and, hence, the overall synthetic methodology utilized to prepare stable high-quality aqueous dispersions of MNPs is a kay factor. 3.4. Cytotoxicity and safety profiles It is crucial to evaluate the cytotoxicity and safety profiles of the PVPylated ferrite NPs before utilizing them for magnetic hyperthermia applications. We focused on the formulations which generated the highest heating efficiencies (i.e. Ni, Co, and Zn-doped ferrites). Thus, the toxicities of various concentrations of MNPs towards a metastatic breast cancer cell lines MDA-MB-231 and KAIMRC-1 57 were evaluated using thiazolyl blue tetrazolium bromide (MTT) viability assay. The MTT assay is based on the capacity of the mitochondrial enzyme of viable cells to transform the MTT tetrazolium salt into a violet-bluish colored MTT formazan, which is proportional to the number of living cells present. As can be seen in Fig. 10 , all doped ferrites were not toxic to MDA-MB-231 or KAIMRC-1 cancerous cells, even at considerably high concentrations (~ 70–80% of the cells remained viable). Interestingly, for PVP-Ni-doped MNP, even when treated with concentrations up to 600 µg/mL, no significant cytotoxicity was observed (> 80% of the cancer cells stayed viable). This repeatedly confirms the safety profiles for magnetite and ferrites, reported by us and others, where even using high concentrations of iron oxide NPs are considered to be safe to the cells with no significant cytotoxicity. This is in accordance with the standardized guidelines for MTT assay in ISO-10993-5 where toxicity is defined as less than 70% viability. Thus, combining the good biocompatibility profiles along with the high heating efficiencies attained suggests that the fabricated PVPylated doped MNPs hold a great potential for magneto-guided in vivo hyperthermia applications. Moreover, as mentioned, all results were obtained under experimental condition Hergt’s limit H. f < 5 × 10 9 A/m − 1 .s − 1 , a limit at which an unwanted nonselective heating of both cancerous as well as healthy tissue may occur, as suggested by Hergt. 4. Conclusion In conclusion, different divalent metal-doped (Ni 2+ , Co 2+ , Zn 2+ , and Mn 2+ ) MFe 2 O 4 NPs with noticeable aqueous stability, small sizes, ferromagnetic behavior, and excellent heating efficiencies were constructed. The magneto-thermal abilities of the MNPs were investigated as function of concentration of MNPs, field amplitude, and frequency. It was found that Ni-doped ferrite NPs showed the highest heating capabilities reaching hyperthermia temperatures (42°C) very fast in ~ 5 min with SAR = 54.74 W/g, where temperatures up to 55°C can be reached. The good heating efficiencies, high SAR values, and low toxicities of the doped MNPs, particularly for Ni and Co-doped magnetite NPs, strongly suggest their promising potential for magnetic hyperthermia applications. Declarations Data Availability The data that supports the findings reported herein are available upon request from the corresponding author. Acknowledgments The authors thank the continuous financial support of the College of Science at University of Bahrain. The authors would like to thank Dr. Dalaver Anjum for conducting the STEM-EELS at Khalifa University of Science and Technology. Author Contributions K.H.B. conceived and designed the study. K.H.B. prepared all the samples. O.M.L. performed the characterization and magnetization of the samples. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3872967","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":269586188,"identity":"70b49332-2837-4cf8-807e-7dc49be61010","order_by":0,"name":"Kheireddine El-Boubbou","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAz0lEQVRIiWNgGAWjYBACCQkeBgbGhgMMDOwNDMwMIDYDDxuRWngOkKxFIoFILZKzew8+5t1xR87g5hvDxwUMNrIbDvAee4BPi7TMuWRj3jPPjA1u5xgbz2BIM95wgC/dAJ8WOYkcM2netsOJG24DGTwMQMYBHjMJ4rTcPAPS8p+wFmm4lhs8IC0HCGuRnJGXbDgX6BfJM2nFxjMMko1nHuZLw6tF4kbuwQdvgSHGd/zwxscFFXayfcd7j+HVggZAQcVMgvpRMApGwSgYBdgBAH8gSq4zRtshAAAAAElFTkSuQmCC","orcid":"","institution":"University of Bahrain","correspondingAuthor":true,"prefix":"","firstName":"Kheireddine","middleName":"","lastName":"El-Boubbou","suffix":""},{"id":269586190,"identity":"85f95fcc-1826-4938-9952-be870f5ad1a2","order_by":1,"name":"O. Mohamed Lemine","email":"","orcid":"","institution":"Imam Muhammad ibn Saud Islamic University","correspondingAuthor":false,"prefix":"","firstName":"O.","middleName":"Mohamed","lastName":"Lemine","suffix":""},{"id":269586191,"identity":"58f75466-4748-4c41-9e10-43bece66aa5b","order_by":2,"name":"Saja Algessair","email":"","orcid":"","institution":"Imam Muhammad ibn Saud Islamic University","correspondingAuthor":false,"prefix":"","firstName":"Saja","middleName":"","lastName":"Algessair","suffix":""},{"id":269586192,"identity":"69dc0ddf-1f36-48e2-ad5e-75b2bcdb4960","order_by":3,"name":"Nawal Madkhali","email":"","orcid":"","institution":"Imam Muhammad ibn Saud Islamic University","correspondingAuthor":false,"prefix":"","firstName":"Nawal","middleName":"","lastName":"Madkhali","suffix":""},{"id":269586193,"identity":"29aa4bdd-e52a-47a0-85cb-2d1315bd451d","order_by":4,"name":"Basma Al-Najar","email":"","orcid":"","institution":"University of Bahrain","correspondingAuthor":false,"prefix":"","firstName":"Basma","middleName":"","lastName":"Al-Najar","suffix":""},{"id":269586194,"identity":"cf27b7fa-e6ae-4875-930a-c490d658a383","order_by":5,"name":"Rizwan Ali","email":"","orcid":"","institution":"King Abdullah International Medical Research Center","correspondingAuthor":false,"prefix":"","firstName":"Rizwan","middleName":"","lastName":"Ali","suffix":""}],"badges":[],"createdAt":"2024-01-17 12:59:12","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-3872967/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3872967/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50281011,"identity":"701bdaa9-2e2c-4a62-bf72-8816c63cf80f","added_by":"auto","created_at":"2024-01-29 04:22:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":173861,"visible":true,"origin":"","legend":"\u003cp\u003eSchematic diagram for the preparation of PVP-coated metal-doped MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e ((M\u0026nbsp;=\u0026nbsp;Co, Ni, Zn, Mn, Sn) NPs using \u003cem\u003eK\u003c/em\u003eo-precipitation \u003cem\u003eH\u003c/em\u003eydrolytic \u003cem\u003eB\u003c/em\u003easic (KHB) methodology.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3872967/v1/fe00b9847e32cd9f3db4a048.png"},{"id":50281433,"identity":"12c5967c-8421-4760-87b9-ec230b10e446","added_by":"auto","created_at":"2024-01-29 04:38:30","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1845294,"visible":true,"origin":"","legend":"\u003cp\u003e(a) TEM and HR-TEM images of the various PVPylated metal-doped MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e samples; (b) corresponding particle-size distribution from the TEM images.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-3872967/v1/375dfadbc7b5e742865bc795.png"},{"id":50281009,"identity":"dab8bc43-cb2b-4cee-9e4f-f2f3055dbfca","added_by":"auto","created_at":"2024-01-29 04:22:30","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1312469,"visible":true,"origin":"","legend":"\u003cp\u003ea) Powder X-ray diffraction patterns of the various PVPylated metal doped MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e samples. b) Rietveld refinement profiles of XRD data of all samples. The red line represents the observed experimental data, and the blue line represents the Rietveld refinement fit. The lower pink curve is the difference between the observed and calculated at each step. The refinements clearly depict the excellent agreement between the observed and calculated patterns.\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-3872967/v1/75a513897e7666b43b0b12a2.png"},{"id":50281187,"identity":"6f09c9d2-37d5-4da9-a4a6-fa8dbcd42fb4","added_by":"auto","created_at":"2024-01-29 04:30:30","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":3002526,"visible":true,"origin":"","legend":"\u003cp\u003ea) Structural model of the primitive unit cell deduced from Rietveld analsyis. b,c) TEM-EDS elemental mapping of (b) PVP-Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e-MNPs, and (c) PVP-CoFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e-MNPs.\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-3872967/v1/961adffa2abe1959104f3660.png"},{"id":50281182,"identity":"cde9b87d-2150-4d8e-abc3-b0f8e939cc06","added_by":"auto","created_at":"2024-01-29 04:30:30","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":110292,"visible":true,"origin":"","legend":"\u003cp\u003eFTIR for the various doped MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e samples clearling showing the successful formation of PVP-coated iron oxide MNPs.\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-3872967/v1/6fb3e7c3d703a13bdeaeaa9d.png"},{"id":50281432,"identity":"33ffe2de-d77e-46e7-9870-a5dedf096e30","added_by":"auto","created_at":"2024-01-29 04:38:30","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":808715,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Field-dependent magnetization hysteresis loops for PVP-ferrite MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs at room temperature; (b) At low field -400 – 400 Oe; c) Law of saturation; (d) Saturation deduced from experimental and LAS fitting.\u003c/p\u003e","description":"","filename":"floatimage7.png","url":"https://assets-eu.researchsquare.com/files/rs-3872967/v1/9b2563a05ee56b5c7ae0bb59.png"},{"id":50281016,"identity":"cf8fc5d5-5a59-420d-afae-557aed6c7ea9","added_by":"auto","created_at":"2024-01-29 04:22:30","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":136482,"visible":true,"origin":"","legend":"\u003cp\u003eHeating efficiencies of PVP-ferrites MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs at different concentrations (2.5, 5, 7.5, and 10 mg/mL) at H= 170 Oe, \u003cem\u003ef\u003c/em\u003e = 332.8 kHz.\u003c/p\u003e","description":"","filename":"floatimage8.png","url":"https://assets-eu.researchsquare.com/files/rs-3872967/v1/3b112199016dde65295a674d.png"},{"id":50281185,"identity":"71dd0ae1-cd55-46ad-afee-1ad027078f63","added_by":"auto","created_at":"2024-01-29 04:30:30","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":61759,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Calculated SAR values for the different doped samples at 10 mg/mL; (b) Correlation between magnetic saturation and SAR values.\u003c/p\u003e","description":"","filename":"floatimage9.png","url":"https://assets-eu.researchsquare.com/files/rs-3872967/v1/95b3e1f545fbed1052ed3169.png"},{"id":50281017,"identity":"648cce01-e7c3-4445-bbcc-b40c93f6e6de","added_by":"auto","created_at":"2024-01-29 04:22:30","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":312642,"visible":true,"origin":"","legend":"\u003cp\u003e(a) Temperature rise at different field amplitude and fixed frequency \u003cem\u003ef\u003c/em\u003e = 332 KHz and (b) corresponding SARs values; (c) Temperature rise at different frequencies and fixed field of H = 170 Oe and (d) corresponding SAR values.\u003c/p\u003e","description":"","filename":"floatimage10.png","url":"https://assets-eu.researchsquare.com/files/rs-3872967/v1/58ae48522b068a068fcb0cf2.png"},{"id":50281434,"identity":"0525343f-120a-4e19-b4d9-3331ac524162","added_by":"auto","created_at":"2024-01-29 04:38:30","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":939492,"visible":true,"origin":"","legend":"\u003cp\u003eMTT cell viability assay for different concentrations of doped MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e MNPs against MDA-MB-231 and KAIMRC1 metastatic breast cancer cells. The results clearly depict the low toxicity and biocompatibility of the various doped ferrite NPs.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e","description":"","filename":"floatimage11.png","url":"https://assets-eu.researchsquare.com/files/rs-3872967/v1/9fb59aa4a217f28d2c6e328f.png"},{"id":50949326,"identity":"708d64a6-011e-4802-abae-d7db5c441294","added_by":"auto","created_at":"2024-02-10 09:59:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":5441634,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3872967/v1/7d56fd22-b3df-45b4-ae7c-a9e67be520fe.pdf"},{"id":50281183,"identity":"9b40947a-ba37-4799-b274-1223c083095a","added_by":"auto","created_at":"2024-01-29 04:30:30","extension":"png","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":283858,"visible":true,"origin":"","legend":"","description":"","filename":"GraphicalAbstract.png","url":"https://assets-eu.researchsquare.com/files/rs-3872967/v1/1d39d0a2b7a4069b41cbc4d5.png"}],"financialInterests":"No competing interests reported.","formattedTitle":"Assessing heating efficiencies of PVPylated divalent metal-doped MFe2O4 nanoparticles for magnetic hyperthermia","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eMagnetic iron oxide nanoparticles (MNPs) have been widely used for biomedical applications in magneto-responsive biomedical applications including biosensing, drug delivery, magnetic resonance imaging (MRI), and magnetic fluid hyperthermia (MFH) \u003csup\u003e1\u0026ndash;4\u003c/sup\u003e. Particularly, in magnetic hyperthermia an implanted magnetic material is utilized under an external alternating magnetic field (AMF) to dissipate heat from MNPs in the area of concern \u003csup\u003e5\u003c/sup\u003e. This approach has become one of the promising potential treatments for cancer as it enables to destroy malignant solid tumors by ablation (T\u0026thinsp;=\u0026thinsp;45\u0026ndash;46 \u003csup\u003e◦\u003c/sup\u003eC) or mild heating (T\u0026thinsp;=\u0026thinsp;40\u0026ndash;45 \u003csup\u003e◦\u003c/sup\u003eC) with minimal side effects. MNPs with their metal (iron (Fe), cobalt (Co), or nickel (Ni) etc.) oxide compartments have been successfully used in this regard \u003csup\u003e6,7\u003c/sup\u003e. They own ferromagnetic and superparamagnetic properties that make them align with the applied magnetic field and, hence, release energy as heat, cooking and killing the target cells selectively.\u003c/p\u003e \u003cp\u003eAmong the various MNPs, magnetite (Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e) is the most commonly studied material for cancer hyperthermia treatment due to its low toxicity, ease of synthesis, and FDA approval \u003csup\u003e8,9\u003c/sup\u003e. It is clearly evident, from our and other reports \u003csup\u003e10\u0026ndash;13\u003c/sup\u003e, that the heating efficiencies of MNPs are affected by several parameters such as size and shape of the NPs, saturation magnetization (M\u003csub\u003e\u003cem\u003es\u003c/em\u003e\u003c/sub\u003e), magnetic anisotropy constant, NP concentration, surface modification as well as the amplitudes and frequency of the applied magnetic field under various experimental conditions. In order to keep improving on the heat dissipated by MNPs, typically computed by specific absorption rate (SAR) and intrinsic loss power (ILP) values, one approach often consists of tuning the magnetic properties of these MNPs by doping the construct with divalent transition metals to prepare ferrite NPs \u003csup\u003e14\u0026ndash;17\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMetal Ferrites MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e (M\u0026thinsp;=\u0026thinsp;Co, Ni, Zn, Mn) are well-studied for magnetic hyperthermia applications, though, with limited outcome \u003csup\u003e15,18\u0026ndash;21\u003c/sup\u003e. The unique ferrite structural stability properties allow more controllable physiochemical properties. This is due to the ability of atom transition between the tetrahedral and octahedral sites within the crystal, which causes alteration in magnetic properties \u003csup\u003e22\u003c/sup\u003e. Moreover, applying different divalent transition metals within the ferrite structure produces distinct magneto-thermal properties depending on their atomic specification (ionic radius and ionic strength) and the amount of ions doped. Hence, different ferrite structures own unique properties such as grain and crystallite sizes as well as different ranges of saturation magnetization, which in turn affects the heating efficiencies \u003csup\u003e23\u003c/sup\u003e. For instance, previous studies have confirmed that Co-ferrite (CoFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e) NPs have a higher saturation magnetization and exhibit greater magnetic properties than magnetite (Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e) due to the presence of Co\u003csup\u003e2+\u003c/sup\u003e ions in the octahedral sites \u003csup\u003e24\u003c/sup\u003e. Moreover, very good heating abilities of various sizes and shapes of Ni-ferrite NPs were reported \u003csup\u003e25 26\u003c/sup\u003e, with the possibility of tuning the SAR values by changing experimental settings. Zinc ferrites were also applied successfully either alone or mixed with Co or Ni in limelight to find their use as heat mediators in magnetic hyperthermia \u003csup\u003e27\u0026ndash;29\u003c/sup\u003e. Moreover, MnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs were also explored as candidates for hyperthermia with reasonably good SAR values \u003csup\u003e30\u003c/sup\u003e. Nonetheless, without proper coating, the usage of such materials is impractical for biomedical applications due to their high toxicity and sensitivity to oxidation.\u003c/p\u003e \u003cp\u003eIt is of immense importance that ferrite NPs are incorporated with polymers to enhance their biocompatibility and stability in physiological media, lower their toxicities, minimize their agglomeration and solution precipitation, and boost their controlled heat dissipation \u003csup\u003e27,31\u003c/sup\u003e. It has been also shown that surface functionalization and polymer coating can enhance the heating efficiencies of the MNPs, in cases where the combination of polymers and metals results in enhanced heat transmission \u003csup\u003e32\u0026ndash;34\u003c/sup\u003e. Metals with excellent thermal conductivity, such as iron oxide NPs, enable efficient heat generation when subjected to an external AMF. The polymer matrix functions as a thermal insulator, preventing excessive heat dissipation and concentrating the generated heat in the target tissue \u003csup\u003e33,35\u0026ndash;37\u003c/sup\u003e. This controlled and localized heating allows for more accurate treatment while reducing damage to neighboring healthy tissues and increasing hyperthermia's therapeutic efficiency \u003csup\u003e34\u003c/sup\u003e. Furthermore, the use of polymer coating the metal cores enables multifunctionality in hyperthermia applications, where polymers can be made to have a variety of features, including biodegradability, biocompatibility, and drug-loading. Thus, for clinical hyperthermia applications, preparation of polymer-coated doped magnetic NPs, MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e (where M\u0026thinsp;\u0026cong;\u0026thinsp;Co, Mn, Ni, or Zn) and decoding their specific magneto-thermal heating capabilities are highly demanded.\u003c/p\u003e \u003cp\u003eHerein, a panel of PVP-coated metal-doped MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e (where M\u0026thinsp;\u0026cong;\u0026thinsp;Co, Mn, Ni, Zn) NPs was prepared using our \u003cem\u003eKo-precipitation Hydrolytic Basic\u003c/em\u003e (KHB) methodology to be utilized for magnetic hyperthermia. We evaluated and studied the magnetic and thermal responses of the various as-prepared PVPylated metal-doped magnetic NPs. We then investigated, systematically, the effects of concentration, field amplitude, and frequency on SAR values for the obtained doped MNPs under safe clinical magnetic field conditions. PVP was chosen as it is widely used in the pharmaceutical industry as a non-ionic water-soluble polymer as dispersant, binder, and suspender. Moreover, we have shown in our previous work the superior heating power of PVP-coated Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs over other employed polymeric magnetite NPs (i.e. PEG, Dextran, HA, and PAA). To the best of our knowledge, this is the first report systematically studying the heating efficiencies of various PVPylated doped MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs for hyperthermia applications.\u003c/p\u003e"},{"header":"2. Experimental Section","content":"\u003cp\u003e\u003cstrong\u003e2.1. Materials and Methods.\u0026nbsp;\u003c/strong\u003eAll chemicals and solvents were obtained from commercial suppliers and used as supplied without further purification. Iron(III) chloride hexahydrate (FeCl\u003csub\u003e3\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO), iron(II) sulfate heptahydrate (FeSO\u003csub\u003e4\u003c/sub\u003e.7H\u003csub\u003e2\u003c/sub\u003eO), Cobalt(II) chloride hexahydrate (CoCl\u003csub\u003e2\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO), \u0026nbsp;Nickel(II) chloride hexahydrate (NiCl\u003csub\u003e2\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO), \u0026nbsp; Zinc chloride hexahydrate (ZnCl\u003csub\u003e2\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO),\u0026nbsp;Stannous chloride\u0026nbsp;hexahydrate (SnCl\u003csub\u003e2\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO), Manganese chloride hexahydrate (MnCl\u003csub\u003e2\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO), Copper(II) chloride hexahydrate (CuCl\u003csub\u003e2\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO), Polyvinylpyrrolidone (PVP Mw ~ 27,000 ), and 28% ammonium hydroxide (NH\u003csub\u003e4\u003c/sub\u003eOH) were all purchased from Sigma Aldrich. All reactions were carried out under inert nitrogen atmosphere.\u003c/p\u003e\n\u003cp\u003eFor biological assays, Dulbecco\u0026rsquo;s Phosphate Buffered Saline (DPBS), Phosphate Buffered Saline (PBS), Advanced Dulbecco\u0026apos;s Modified Eagle Medium (DMEM), Phenol-red free DMEM, Fetal Bovine Serum (FBS), Hoechst 33342 stain, L-Glutamine, and Penicillin-Streptomycin (Pen-Strep) were all purchased from Invitrogen. MTT (Thiazolyl Blue Tetrazolium Bromide) powder was purchased from Bioworld, USA. All cell lines were purchased from the American Type Culture Collection (ATCC) and grown in Advanced DMEM supplemented with 10% FBS and 1% Penicillin/Streptomycin. Human cancerous cells used in this study are:\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003eMDA-MB-231 (metastatic breast cancer cell line) and KAIMRC1 (naturally immortalized\u0026nbsp;KAIMRC1 breast cancer cells isolated from a 62-year-old Arab female suffering from stage IIB breast cancer).\u0026nbsp;All experiments were conducted in triplicates and mean.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCharacterization\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eX-ray diffraction (XRD) using Rigaku Uitima IV equipped with Cu-K\u0026alpha; radiation source (0.15418 nm) with angle ranging from 10⁰ to 80⁰ and the crystal structure parameters were obtained through Rietveld analysis. The morphology of the samples was studied by means of transmission electron microscope (TEM). TEM micrographs of the MNPs were obtained using a Titan 300 kV ST (FEI) electron microscope. Prior to TEM imaging, we treated the TEM grids with plasma to remove organics and dust. For TEM imaging, a few drops of the doped MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e samples were drop-casted on the TEM grids and dried under vacuum. Compositional and chemical analysis were performed on the samples using core-loss electron energy loss spectroscopy (EELS) in nanoscale. Fourier\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003etransform infrared (FTIR) spectra (400\u0026ndash;4000 cm-1) were recorded as KBr pellet forms using Shimadzu IRAffinity-1. Magnetic characterizations were performed using vibrating sample magnetometer (VSM) with 1.8 T magnets at ambient temperature.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.2. Preparation of PVP-coated MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/strong\u003e\u003csub\u003e\u0026nbsp;\u003c/sub\u003e\u003cstrong\u003eNPs\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eby KHB method.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll MNPs were prepared using our previously reported \u003cem\u003eKHB\u0026nbsp;\u003c/em\u003emethod as illustrated in \u003cstrong\u003eFig. 1\u003c/strong\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFeCl\u003csub\u003e3\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO (0.30 g) was mixed with PVP (0.2 g) dissolved in\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003ewater (10 mL) and stirred for few minutes\u0026nbsp;at 80 \u0026deg;C\u0026nbsp;under nitrogen. FeSO\u003csub\u003e4\u003c/sub\u003e.7H\u003csub\u003e2\u003c/sub\u003eO: MCl\u003csub\u003e2\u003c/sub\u003e.6H\u003csub\u003e2\u003c/sub\u003eO (0.1 g: 0.1 g) dissolved in water was then injected into the above solution. Ammonium hydroxide NH\u003csub\u003e4\u003c/sub\u003eOH 28 % (~ 3 mL) was slowly added where the solution turned black-brick colored depicting the formation of doped MNPs. Stirring was continued for 24 hrs to allow better crystalline phases. The NP suspensions were then purified \u003cem\u003evia\u003c/em\u003e centrifugation (4500 rpm, 5 min), washed several times with isopropanol, ethanol, and water, and finally re-dispersed in water to afford stable aqueous dispersions of PVP-coated doped MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs. For the preparation of Fe3O4 MNPs, same procedure was followed using 0.2 g of Fe\u003csup\u003e2+\u003c/sup\u003e precursor. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.3. Evaluation of Heating Efficiencies\u003c/strong\u003e. The heating efficiency of the samples was performed using a commercial system \u0026quot;Nanotherics Magnetherm\u0026quot; as reported in our previous works \u003csup\u003e13,18,33\u003c/sup\u003e. Different concentrations (10, 7.5, 5, and 2.5 mg/mL) of doped MNPs have been investigated at 170 Oe and 332.8 kHz for the field amplitude and frequency, respectively. The samples were dissolved in distilled water and sonicated for 10 min and the temperature increase of the samples was then recorded for 15 min.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e2.4. Cell Viability Assay\u003c/strong\u003e.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eCell viability of breast cancer MDA-MB231 and KAIMRC1 cells exposed to different concentration of MNPs was determined using MTT assay. The cell lines were seeded in a 96-well plate at a density of 5 \u0026times; 10\u003csup\u003e5\u003c/sup\u003e cells/ well and incubated in 95%/5% humidified air/CO\u003csub\u003e2\u003c/sub\u003e at 37 \u0026deg;C. After overnight incubation, cells were treated with various concentrations of control and metal-doped samples in 100 \u0026mu;L of supplemented DMEM. After 48 h of incubation, the medium was removed, and the cells were washed with PBS. Then, 5 \u0026mu;L of MTT reagent (5 mg/mL) was added to each well and kept for 4 h at 37 \u0026deg;C in the incubator. The supernatant was then removed, and 100ul of dimethyl sulfoxide (DMSO) was added to each well. The absorbance was measured on the Molecular Devices Spectrophotometer absorbance reader at 590 nm. The percentage of viable cells was calculated as the ratio of the absorbance of the treated group divided by the absorbance of the control group multiplied by 100.\u003c/p\u003e"},{"header":"3. Results and Discussion","content":"\u003cp\u003e\u003cstrong\u003e3.1. Preparation and characterization of MFe\u003c/strong\u003e \u003csub\u003e\u0026nbsp;\u003cstrong\u003e2\u003c/strong\u003e\u0026nbsp;\u003c/sub\u003e \u003cstrong\u003eO\u003c/strong\u003e \u003csub\u003e\u0026nbsp;\u003cstrong\u003e4\u003c/strong\u003e\u0026nbsp;\u003c/sub\u003e \u003cstrong\u003eMNPs.\u003c/strong\u003e All MNPs were prepared using our previously reported \u003cem\u003eKHB\u003c/em\u003e method as illustrated in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Briefly, sequential \u003cem\u003ein situ\u003c/em\u003e basic hydrolytic precipitation of iron salts (Fe\u003csup\u003e3+\u003c/sup\u003e and M\u003csup\u003e2+\u003c/sup\u003e: Fe\u003csup\u003e2+\u003c/sup\u003e; 1:1) in the presence of PVP afforded stable aqueous dispersions of PVP-coated metal-doped MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e-MNPs. The obtained doped MNPs were characterized by various electronic and spectroscopic techniques including TEM, XRD, and VSM. These techniques clearly revealed the structure, morphology, and magnetization of the as-synthesized MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs. TEM images (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003ea) clearly indicated the quasi-spherical morphology of all ferrite NPs, with average sizes of 10 nm except for Ni ferrite NPs (sizes\u0026thinsp;~\u0026thinsp;17 nm) as depicted by their corresponding particle size-distribution (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003eb). High-resolution TEM (HR-TEM) indicates that the NPs show close-packed 2D array of relatively uniform sized particles clearly showing the interfringe lattices of the NPs. Each particle is a well-ordered single crystal despite their small size. In fact, the distance between two adjacent lattice fringes obtained by HR-TEM analysis of a single nanocrystal is calculated to be ~\u0026thinsp;0.25 nm corresponding to the lattice spacing of (311) planes of magnetite \u003csup\u003e38\u003c/sup\u003e. To elucidate the crystalline structure and identify which phase we have, XRD was performed. XRD patterns of all MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e samples are illustrated in Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003ea, showing well-crystallized inverse spinel structures. Well-defined peaks are observed for each spectrum indicating the crystalline nature of the samples. For all samples, main peaks were defined at (220), (311), (400), (422), (511), (440), and (533) which are related to the spinel structure. Both Co and Ni ferrite possess a fully inverse structure due to the chemical nature of Ni\u003csup\u003e2+\u003c/sup\u003e and Co\u003csup\u003e2+\u003c/sup\u003e which tend to occupy octahedral sites while Fe\u003csup\u003e3+\u003c/sup\u003e occupy tetrahedral ones \u003csup\u003e39\u003c/sup\u003e. Rietveld analysis of these XRD spectra confirmed the formation of pure MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e cubic spinel phases with space group Fd3m for NiFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4,\u003c/sub\u003e CoFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e, ZnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e, and MnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e which matches well with JCPDS # 01-071-3850, # 01-074-6402, # 01-071-5149, and # 01-071-4919, respectively. The refinements show an excellent agreement between the observed and calculated patterns (Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eb). No additional peaks have been observed suggesting that the synthetic method leads to the formation of a pure spinel ferrite phase. From Rietveld analysis of XRD results, the crystallite size, microstrain, and lattice parameters of all samples were calculated as shown in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. Different sizes of crystals were formed depending on the metal ferrite ranging from 5.2 nm for MnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e to 18.5 nm for NiFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e. Such variation in crystallite size between different metal ferrites might be due to the difference in the ionic radii of the dopant metals\u003csup\u003e40\u003c/sup\u003e. The lattice parameters also varied but slightly from 1.13 to 0.09. The unit cell of the MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e ferrite structures deduced from Rietveld shows that iron ions are tetrahedrally and octahedrally coordinated to oxygens, where doping with M\u003csup\u003e2+\u003c/sup\u003e did not alter much either the crystal structure or the lattice parameter (Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003ea). This is expected as the substitution of Fe\u003csup\u003e3+\u003c/sup\u003e ions by very small amounts of M\u003csup\u003e2+\u003c/sup\u003e ions ((Fe\u003csup\u003e3+\u003c/sup\u003e: M\u003csup\u003e2+\u003c/sup\u003e; 3: 1) would not induce geometrical distortion in the unit cell\u003csup\u003e18\u003c/sup\u003e. Regarding SnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e sample, the XRD spectra indicated less crystallinity as the peaks were not sharp. The Rietveld analysis showed its best match with the orthogonal Sn\u003csub\u003e0.096\u003c/sub\u003eFe\u003csub\u003e1.874\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e phase. TEM-EDS elemental analysis was then performed to further confirm the purity of the as-synthesized doped samples. For instance, the presence of Fe, O, C, and Co peaks for Co-doped ferrite NPs without any additional element reveal the high purity of the obtained ferrites. The spatial distribution of each component within the NPs was investigated using the STEM-EDS spectrum imaging (SI) method,\u003csup\u003e41\u003c/sup\u003e and the obtained elemental mappings of the elements are shown in Fig. \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003eb,c. The uniform distribution was observed in the generated map of each element. Each sample\u0026apos;s black and white image represents the High Angle Annular Dark Field (HAADF) imaging, while the red, green, cyan, and blue colors represent Fe, O, C, and Co elements, respectively. The lower brightness of the C element explains the decrease of its atomic percentage compared to Fe, Co, or O.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eRietveld analysis results of XRD spectra of PVPylated MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSample\u003c/p\u003e\n \u003cp\u003e(Phase %)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDB card No.\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSize (nm)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMicro\u003c/p\u003e\n \u003cp\u003estrain\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLattice Parameter (A\u003csup\u003e◦\u003c/sup\u003e)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003eFitting Parameters\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePVP-Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e01-071-6337\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.314 (7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ea:8.344\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRwp:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e41.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRp:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31.06\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRe:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e37.85\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eb:8.344\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ec:8.344\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eS:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePVP-NiFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e01-071-3850\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.093 (6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ea:8.355\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRwp:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRp:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRe:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e36.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eb:8.355\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ec:8.355\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eS:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.0441\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePVP-CoFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.09\u003c/p\u003e\n \u003cp\u003e(7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ea:8.379\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRwp:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e41.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRp:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e30.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRe:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e41.61\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e01-074-6402\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eb:8.379\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ec:8.379\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eS:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.9915\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.983\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePVP-ZnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e01-071-5149\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.343 (12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ea:8.436\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRwp:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRp:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRe:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22.91\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eb:8.436\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ec:8.436\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eS:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePVP-MnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e01-071-4919\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.13\u003c/p\u003e\n \u003cp\u003e(4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ea:8.355\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRwp:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRp:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRe:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e27.24\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e(100%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eb:8.355\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ec:8.355\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eS:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePVP-Sn\u003csub\u003e0.09\u003c/sub\u003e6Fe\u003csub\u003e1.874\u003c/sub\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e01-088-0432\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.58\u003c/p\u003e\n \u003cp\u003e(6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ea:5.093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRwp:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRp:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRe:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e19.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eb:5.093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ec:13.93\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eS:\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2.05\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003eNext, FTIR analysis was conducted to further validate the successful formation of PVP-coated MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs (Fig. \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). The presence of iron oxide (Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e) in the core was clearly evident by the Fe\u0026thinsp;\u0026minus;\u0026thinsp;O stretching bands at 560 and 620 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, which appeared as one broad peak\u0026thinsp;~\u0026thinsp;560\u0026ndash;600 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e for the MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e because of metal doping the crystallites. The distinctive peaks at 2850 and 2920 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e clearly depict the symmetric and asymmetric C-H stretching modes of PVP coating, while the broad peak at ~\u0026thinsp;3400 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e is ascribed to the O\u0026thinsp;\u0026minus;\u0026thinsp;H stretching vibration of hydroxyl groups on MNPs. Another major signature peak is the stretching vibration of C\u0026thinsp;=\u0026thinsp;O carbonyl evident at ~\u0026thinsp;1635 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e. The carbonyl of free PVP polymer typically appears at 1660 cm\u003csup\u003e\u0026minus;\u0026thinsp;1 42,43\u003c/sup\u003e. This shift from 1660 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e to 1635 cm\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e confirms the functionalization of MNPs with PVP \u003cem\u003evia\u003c/em\u003e intermolecular hydrogen bonding between the carbonyl group of PVP and the protonated hydroxyl groups on MNP surfaces. Moreover, PVP is well-known to adsorb on the ferrite nanocrystals \u003cem\u003evia\u003c/em\u003e coordinative bonds between the pyrrolidone molecules and the metal ions, where the donated lone pairs of both nitrogen and oxygen atoms form complex with Fe\u003csup\u003e3+\u003c/sup\u003e ions \u003csup\u003e44\u003c/sup\u003e. All these results clearly indicate the successful coating of MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e ferrite NPs with PVP.\u003c/p\u003e\n\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\n \u003ch2\u003e3.2. Magnetic Properties\u003c/h2\u003e\n \u003cp\u003eTo determine the magnetic behavior of the MNPs, field-dependent magnetizations were conducted. The coating and doping can both have dominant effects on magnetization and, hence, the heating efficiencies of MNPs. Figure \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003ea depicted the hysteresis loop (M\u0026ndash;H) of the as-synthesized MNPs at 300 K, while saturation (M\u003csub\u003er\u003c/sub\u003e), coercivity (H\u003csub\u003ec\u003c/sub\u003e), and remanence (M\u003csub\u003er\u003c/sub\u003e) values deduced from the loops are summarized in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. It can be observed that all ferrite NPs behave as soft ferromagnetic with small but non-negligible coercivity and remanence (Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003eb). The saturation magnetization (\u003cem\u003eM\u003c/em\u003e\u003csub\u003e\u003cem\u003es\u003c/em\u003e\u003c/sub\u003e) obtained for the PVP-NiFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e, PVP-CoFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eNPs, PVP-ZnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e, PVP-MnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e, and PVP-SnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e ferrite NPs were found to be equal to 80.74, 66.17, 38.78, 26.26, 4.26 emu/g respectively. As evident the highest saturation magnetizations were found for Ni and Co-doped samples with the lowest obtained for Sn-doped iron oxide sample. This huge difference between saturation can be caused by several factors such as the type of spinel ferrites in which the synthesized samples are crystallized, the magnetic nature of the divalent cations (i.e. Co\u003csup\u003e2+\u003c/sup\u003e, Ni\u003csup\u003e2+\u003c/sup\u003e, Zn\u003csup\u003e2+\u003c/sup\u003e, Mn\u003csup\u003e+\u0026thinsp;2\u003c/sup\u003e, and Sn\u003csup\u003e2+\u003c/sup\u003e), their distribution in the octahedral and tetrahedral sites, size of NPs obtained, and the presence of magnetic dead layers due to the coating of the ferrite NPs by PVP. Co and Ni are ferromagnetic and interaction between Co or Ni ions spin and the lattice favors the alignment of their spins parallel to the cube edge of the spinel lattice. In addition, both ions induce uniaxial magnetic anisotropy in the magnetization direction which will increase saturation. Other divalent cations are non-magnetic where the insertion of these ions in the octahedral sites will affect Fe-ions interactions and induce decrease in long range magnetic ordering, which explained the low saturation. Importantly, the PVP-coated MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e ferrite NPs obtained here have relatively high saturation magnetizations, which are larger than similar polymer-coated ferrite MNPs reported in the literature \u003csup\u003e44\u0026ndash;47\u003c/sup\u003e, indicating high degree of magnetic ordering and crystallinity. For instance, Oulhakem et al. reported saturation of 18.43, 13.53, and 0.69 emu/g for alginate-encapsulated Alg@CoFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e, Alg@NiFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e, and Alg@ZnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e respectively \u003csup\u003e28\u003c/sup\u003e. Interestingly, most studies reported decrease of saturation after coating of NPs by organic polymer/matrix \u003csup\u003e28,48\u003c/sup\u003e, while coating with PVP tends to increase the saturation of ferrite NPs (i.e. 80.74 emu/g for PVP-NiFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e) and magnetite NPs \u003csup\u003e33\u003c/sup\u003e.\u003c/p\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMagnetic parameters deduced from M-H curves and law of approach saturation.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003eExperimental\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eLaw of saturation (LAS)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSample\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eH\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003ec\u003c/strong\u003e\u003c/sub\u003e \u003cstrong\u003e(Oe)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eM\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003er\u003c/strong\u003e\u003c/sub\u003e \u003cstrong\u003e(emu)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eM\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003es\u003c/strong\u003e\u003c/sub\u003e \u003cstrong\u003e(emu/g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eM\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003er\u003c/strong\u003e\u003c/sub\u003e\u003cstrong\u003e/M\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003es\u003c/strong\u003e\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eM\u003c/strong\u003e\u003csub\u003e\u003cstrong\u003es\u003c/strong\u003e\u003c/sub\u003e \u003cstrong\u003e(emu/g)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eK\u003csub\u003eeff\u003c/sub\u003e\u003c/p\u003e\n \u003cp\u003e(erg/cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePVP-Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39.70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.5857\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePVP-NiFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e80.74\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e80.79\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.182\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePVP-CoFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e218\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e9.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e66.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.75\u0026times;10\u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePVP-ZnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e39.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.1038\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePVP-MnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16.64\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e25.97\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.0767\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePVP-SnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.08\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e4.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.50361\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eIn addition to the saturation magnetization, there are three magnetic parameters, which affect the heating ability for hyperthermia application, namely: coercivity (H\u003csub\u003ec\u003c/sub\u003e), remanence (M\u003csub\u003er\u003c/sub\u003e) and magnetic anisotropy constant (K\u003csub\u003eeff\u003c/sub\u003e). The coercivity is affected by the nature of the magnetic nature of the divalent cations and reached the highest value of 218 Oe for PVP-CoFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs. Regarding the remanence, the ratio (M\u003csub\u003er\u003c/sub\u003e/M\u003csub\u003es\u003c/sub\u003e) values are in the range 0.01\u0026ndash;0.14 which deviates largely from the value of 0.5 suggested by Stoner-Wolfahrt\u0026rsquo;s model \u003csup\u003e49\u003c/sup\u003e, for an ensemble of non-interacting single domain magnetic particles distributed randomly. The deviation from the theoretical value M\u003csub\u003er\u003c/sub\u003e/M\u003csub\u003es\u003c/sub\u003e = 0.5 could be attributed to the effect of dipolar interactions which reduces the remanence.\u003c/p\u003e\n \u003cp\u003eFinally, the effective anisotropy constant (K\u003csub\u003eeff\u003c/sub\u003e) was deduced from the fitting of the experimental magnetization as shown in Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003ec by using the following Eq.\u0026nbsp;5\u003csup\u003e0\u003c/sup\u003e:\u003c/p\u003e\n \u003cdiv id=\"Equa\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e$$\\text{M}\\left(\\text{H}\\right)={\\text{M}}_{\\text{s}}\\left(1-\\frac{\\text{b}}{{\\text{H}}^{2}}\\right) \\left(1\\right)$$\u003c/div\u003e\n \u003c/div\u003e\n \u003cp\u003ewhere b is a parameter which is deduced from the fitting of experimental magnetization with Eq. (1). K\u003csub\u003eeff\u003c/sub\u003e is then determined by Eq. (2) as follows \u003csup\u003e51\u003c/sup\u003e:\u003c/p\u003e\n \u003cdiv id=\"Equb\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equb\" name=\"EquationSource\"\u003e$${\\text{K}}_{\\text{e}\\text{f}\\text{f}}={{{\\mu }}_{0}\\text{M}}_{\\text{s}}\\sqrt{\\frac{15\\text{b}}{4}} \\left(2\\right)$$\u003c/div\u003e\n \u003c/div\u003e\n \u003cp\u003eThe calculated values of K\u003csub\u003eeff\u003c/sub\u003e are summarized in the Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. It can be observed that the highest value (2.75\u0026times;10\u003csup\u003e5\u003c/sup\u003e erg/cm\u003csup\u003e3\u003c/sup\u003e) is obtained for PVP-CoFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs which shows the highest coercivity (218 Oe). It can be also noticed that saturation deduced from the fit is slightly different from the experimental values indicating the accuracy of the fitting by LAS (Fig. \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003ed).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\n \u003ch2\u003e3.3. Magnetic Hyperthermia Measurements\u003c/h2\u003e\n \u003cp\u003eThe heating performance of MNPs is intimately entwined with their structure, size, and magnetic anisotropy. For magnetic hyperthermia, the main challenges lie in obtaining NPs of specific characteristics: high heating efficiencies with minimal concentrations under clinically safe field exposure. When a magnetic system is subjected to AMF, heat is generated due to certain loss mechanisms, which can be classified as hysteresis and relaxation losses. It was specifically found that SAR values for superparamagnetic/ferromagnetic NPs (almost negligible hysteresis losses) are directly affected by parameters which influence the magnetic moment rotation responsible for heat dissipated through Brownian and N\u0026eacute;el relaxation mechanisms \u003csup\u003e51\u0026ndash;53\u003c/sup\u003e. Frequency and field amplitude of AMF also have direct effects on the heating efficiencies of the MNPs. For clinical hyperthermia applications and to satisfy medical safety conditions, there are two limitations for the product of the amplitude (H) and the frequency (\u003cem\u003ef\u003c/em\u003e) for the applied magnetic field known as the Atkinson\u0026thinsp;\u0026minus;\u0026thinsp;Brezovich limit (H\u0026times;\u003cem\u003ef\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;4.85 \u0026times; 108 A.m\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e.s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e) and the Hergt\u0026rsquo;s limit (H\u0026times;\u003cem\u003ef\u003c/em\u003e\u0026thinsp;\u0026le;\u0026thinsp;5\u0026times;10\u003csup\u003e9\u003c/sup\u003e A.m\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e.s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e) \u003csup\u003e54,55\u003c/sup\u003e. Thus, for an efficient clinical utilization of MNPs in hyperthermia, the heat dissipation should be optimized by using minimal dosage of polymer-coated MNPs (to ensure biocompatibility) and high magnetic properties (to guarantee efficient heating) in relatively short times. Therefore, designing tailored doped ferrite NPs that can dissipate heat at low concentrations under different ranges of frequencies and magnetic field is key to achieve a controllable and efficient hyperthermia treatments. Moreover, preparing stabilized well-dispersed magnetic NPs with high heating efficiencies and SAR values in large quantities in an easy, robust, cheap, and reproducible process is likewise demanded.\u003c/p\u003e\n \u003cp\u003eThe heating efficiencies of PVPylated undoped and doped ferrite NPs dispersed in water under alternating magnetic field (AMF) were evaluated. Figure \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e shows the temperature rise of aqueous dispersions of various doped ferrite NPs at different concentrations under AMF with frequency and amplitude of 332.8 kHz and 170 Oe, respectively. The main parameters that assess self-heating abilities of MNPs obtained from the temperature rise are summarized in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. As can be observed from Fig. \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e, MNPs show high heating abilities and reach magnetic hyperthermia temperatures (42\u0026deg;C) in relatively short times. Within 15 min, the solution with the highest concentration (10 mg/mL) reached, noticeably, higher temperatures, in comparison with 7.5, 5, and 2.5 mg/mL solutions. This dependence of the temperature rise on the concentration of NPs is expected because more heat generators (i.e. NPs) are present in the concentrated sample. The temperatures for all the samples slowly increased but did not reach saturation within the 15 min period. During the magnetic hyperthermia treatment, the temperature should be regulated at 42\u0026deg;C for at least 30 min to kill the malignant tumor, but it should be also kept below 46\u0026deg;C to prevent normal tissues from burning. Thus, all the tested doped ferrite samples (7.5 and 10 mg/mL) satisfy these conditions, particularly the PVPylated Ni- and Co-Fe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs. Interestingly, even for lower concentrations of 2.5 mg/ml, Ni-doped sample indicated a very good temperature rise and reached hyperthermia temperatures.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 3. Heating parameters for the different doped PVP-MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs at various concentrations (H = 170 Oe, \u003cem\u003ef\u003c/em\u003e = 332.8 kHz).\u003c/strong\u003e\u003c/p\u003e\n \u003cdiv align=\"\"\u003e\n \u003ctable dir=\"rtl\" border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"707\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.164073550212164%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eILP (nHm\u003csup\u003e2\u003c/sup\u003e/kg)\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e(2-15 sec)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.831683168316832%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eSAR (W/g)\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e(2-15 sec)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.874115983026876%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eTime needed to reach 42 ⁰C (min)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.71994342291372%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eMaximum temperature\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e(⁰C)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.275813295615276%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eConcentration\u003c/strong\u003e\u003c/p\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e(mg/mL)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.134370579915135%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003eSample\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.164073550212164%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e0.498\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.831683168316832%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e30.253\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.874115983026876%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e5.57\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.56859971711457%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"RTL\"\u003e53.97\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.427157001414427%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.134370579915135%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003ePVP-Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.353\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e21.456\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e9.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e47.42\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.456\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e27.679\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eNot reaching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e40.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.487\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e29.610\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eNot reaching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e34.37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.164073550212164%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e0.503\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.831683168316832%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e30.575\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.874115983026876%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e11.15\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.56859971711457%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e48.53\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.427157001414427%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.134370579915135%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003ePVP-CoFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.396\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e24.031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e11.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e45.31\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.372\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e22.759\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e13.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e43.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.330\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e20.897\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eNot reaching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e38.93\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.164073550212164%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e0.900\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.831683168316832%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e54.714\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.874115983026876%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e5.20\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.56859971711457%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e55.50\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.427157001414427%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.134370579915135%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003ePVP-NiFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.840\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e51.066\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e5.73\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e54.66\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.636\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e38.622\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e8.93\u003c/span\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e48.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.593\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e36.047\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e11.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e44.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.164073550212164%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e0.387\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.831683168316832%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e23.495\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.874115983026876%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e10.07\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.56859971711457%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e45.99\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.427157001414427%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.134370579915135%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003ePVP-ZnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.257\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e17.165\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e13.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e43.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.413\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e25.104\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e14.41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e42.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.283\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e19.909\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eNot reaching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e35.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.164073550212164%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e0.339\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.831683168316832%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e20.598\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.874115983026876%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e8.58\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.56859971711457%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e45.50\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.427157001414427%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.134370579915135%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003ePVP-MnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.354\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e19.161\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e11.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cspan dir=\"RTL\"\u003e4\u003c/span\u003e0.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.230\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e14.311\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eNot reaching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e38.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.208\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e12.185\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eNot reaching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e35.16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"12.164073550212164%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e0.302\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"16.831683168316832%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"RTL\"\u003e18.345\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.874115983026876%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e12.35\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.56859971711457%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e\u003cspan dir=\"RTL\"\u003e43.98\u003c/span\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.427157001414427%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003e10\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"15.134370579915135%\" rowspan=\"4\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e\u003cstrong\u003ePVP-SnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.212\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e12.874\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eNot reaching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e38.90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e7.0810\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eNot reaching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e35.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"14.333333333333334%\" valign=\"bottom\"\u003e\n \u003cp dir=\"LTR\"\u003e0.187\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.833333333333332%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e9.610\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.666666666666668%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003eNot reaching\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.166666666666668%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e33.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17%\" valign=\"top\"\u003e\n \u003cp dir=\"LTR\"\u003e2.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003cp\u003eSAR values, defined as the dissipation heat generated by a unit mass of MNPs, were then determined by Eq.\u0026nbsp;(3) as follows:\u003c/p\u003e\n \u003cdiv id=\"Equc\" class=\"Equation\"\u003e\n \u003cdiv class=\"mathdisplay\" id=\"FileID_Equc\" name=\"EquationSource\"\u003e$$SAR=\\frac{{\\rho C}_{w}}{{Mass}_{MNP}}\\left(\\frac{{\\Delta }T}{{\\Delta }t}\\right)\\left(3\\right)$$\u003c/div\u003e\u003c/div\u003e\u003cp\u003ewhere C\u003csub\u003ew\u003c/sub\u003e is defined as the specific heat capacity of water (4.185 J/g.k), the density of the colloid is \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\rho\\)\u003c/span\u003e\u003c/span\u003e, the concentration of MNPs in the suspension is called \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\({Mass}_{MNP}\\)\u003c/span\u003e\u003c/span\u003e and the heating rate is represented by \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\frac{{\\Delta }T}{{\\Delta }t}\\)\u003c/span\u003e\u003c/span\u003e. By performing a linear fit of temperature increase \u003cem\u003evs\u003c/em\u003e time at the initial time interval (1 to 30 s), the slope\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\Delta T/\\Delta t\\)\u003c/span\u003e\u003c/span\u003eis obtained. The calculated SAR values are summarized in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. The relatively high values indicate the good heating capabilities of the prepared ferrite NPs. There is a significant increase of SAR for PVP-NiFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs (~\u0026thinsp;55 W/g) compared to other samples, which is relatively higher than that of other similar reported doped magnetic NPs. It can be noted also from the table, that SAR decreases with decreasing concentration of MNPs. This is in agreement with our previous work,\u003csup\u003e33\u003c/sup\u003e where the dependence of the temperature rise on the concentration is expected as more heat generators are present in the concentrated samples. In addition, important parameters such as the core sizes, viscosity of the medium, and polydispersity of the samples can considerably affect SAR. Such behavior could be directly attributed to enhancement in the interparticle dipolar interactions, which influences N\u0026eacute;el-Brownian relaxation \u003csup\u003e56\u003c/sup\u003e. Comparison of SAR values at 10 mg/mL concentration (Fig. \u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003ea), shows that PVP-NiFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs have the highest value (54.71W/g), while PVP-SnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs indicate the lowest value (18.34 W/g). Difference in SAR values can be explained by the effect of many parameters as indicated above but saturation anisotropy remains the main parameter which directly affects the heating ability. Figure \u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003eb shows that there is direct correlation between SAR and M\u003csub\u003es\u003c/sub\u003e values, where MNPs with the highest magnetic saturation (PVP-NiFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs) resulted in the highest SAR, while the one with lowest saturation is recorded for PVP-SnFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs. Thus, it can be clearly concluded that there are optimal parameters that should be produced (size, magnetization, polydispersity, coating, concentration etc) to maximize SAR values for MNPs.\u003c/p\u003e\u003cp\u003eFinally, the effects of both the field amplitude and the frequency on self-heating ability of PVP-NiFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs (10 mg/mL) was then investigated. Different combinations of magnetic fields and frequencies were applied. In Fig. \u003cspan class=\"InternalRef\"\u003e9\u003c/span\u003ea, the frequency was fixed at 332 kHz and the magnetic field varied to 130, 150 and 170 Oe. It can be seen that the temperature rise increases with increasing field amplitude. Magnetic hyperthermia temperature (42\u0026deg;C) is not reached at 130 Oe, however increasing the magnetic field to 170 Oe caused a clear rise in temperature allowing the reach of 42\u0026deg;C. SAR values were increased with increasing field amplitude (Fig. \u003cspan class=\"InternalRef\"\u003e9\u003c/span\u003eb). Similar behavior is observed when the frequency was adjusted to 113, 170 and 332 kHz, while the field was fixed to 120 Oe as shown in Fig. \u003cspan class=\"InternalRef\"\u003e9\u003c/span\u003ec,d. Overall, for all applied frequencies, the maximum temperature reached by the NPs is increasing with field amplitude, leading to higher SAR values. As shown previously in Eq.\u0026nbsp;3, the calculation of SAR values depends on the initial slope of temperature rise. We can conclude that applying different combinations of frequencies and magnetic allows the tuning of self-heating characteristics of the MNPs.\u003c/p\u003e\u003cp\u003eFinally, the intrinsic loss power (ILP), used to compare the heating efficiencies of different MNPs were calculated by using the obtained values of SAR and applying the following equation:\u003c/p\u003e\u003cdiv id=\"Equ1\" class=\"Equation\"\u003e\u003cdiv class=\"mathdisplay\" id=\"FileID_Equ1\" name=\"EquationSource\"\u003e$$ILP=SAR/fH_{0}^{2}$$\u003c/div\u003e\u003cdiv class=\"EquationNumber\"\u003e4\u003c/div\u003e\u003c/div\u003e\u003cp\u003ewhere \u003cem\u003ef\u003c/em\u003e is the frequency and H\u003csub\u003e0\u003c/sub\u003e is the coercivity\u003c/p\u003e\u003cp\u003eThe ILP values for different concentrations of doped MNPs under the different sets of experimental conditions and various concentrations are summarized in Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e. As can be observed, these values are comparable to that reported for maghemite [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e], magnetite [\u003cspan class=\"CitationRef\"\u003e21\u003c/span\u003e] and commercials ferrofluids [\u003cspan class=\"CitationRef\"\u003e22\u003c/span\u003e]. All these results indicated that the heat dissipated by MNPs can be tuned easily by changing the concentration, field amplitude, and frequency of the AMF as reported by many other systems [\u003cspan class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]. Such tuning depends mainly on the magnetic properties, particle size, crystallinity, interparticle interactions, dispersing medium, and, hence, the overall synthetic methodology utilized to prepare stable high-quality aqueous dispersions of MNPs is a kay factor.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e3.4. Cytotoxicity and safety profiles\u003c/h2\u003e\u003cp\u003eIt is crucial to evaluate the cytotoxicity and safety profiles of the PVPylated ferrite NPs before utilizing them for magnetic hyperthermia applications. We focused on the formulations which generated the highest heating efficiencies (i.e. Ni, Co, and Zn-doped ferrites). Thus, the toxicities of various concentrations of MNPs towards a metastatic breast cancer cell lines MDA-MB-231 and KAIMRC-1\u003csup\u003e57\u003c/sup\u003e were evaluated using thiazolyl blue tetrazolium bromide (MTT) viability assay. The MTT assay is based on the capacity of the mitochondrial enzyme of viable cells to transform the MTT tetrazolium salt into a violet-bluish colored MTT formazan, which is proportional to the number of living cells present. As can be seen in Fig. \u003cspan class=\"InternalRef\"\u003e10\u003c/span\u003e, all doped ferrites were not toxic to MDA-MB-231 or KAIMRC-1 cancerous cells, even at considerably high concentrations (~\u0026thinsp;70\u0026ndash;80% of the cells remained viable). Interestingly, for PVP-Ni-doped MNP, even when treated with concentrations up to 600 \u0026micro;g/mL, no significant cytotoxicity was observed (\u0026gt;\u0026thinsp;80% of the cancer cells stayed viable). This repeatedly confirms the safety profiles for magnetite and ferrites, reported by us and others, where even using high concentrations of iron oxide NPs are considered to be safe to the cells with no significant cytotoxicity. This is in accordance with the standardized guidelines for MTT assay in ISO-10993-5 where toxicity is defined as less than 70% viability. Thus, combining the good biocompatibility profiles along with the high heating efficiencies attained suggests that the fabricated PVPylated doped MNPs hold a great potential for magneto-guided \u003cem\u003ein vivo\u003c/em\u003e hyperthermia applications. Moreover, as mentioned, all results were obtained under experimental condition Hergt\u0026rsquo;s limit H.\u003cem\u003ef\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;5 \u0026times; 10\u003csup\u003e9\u003c/sup\u003e A/m\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e.s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, a limit at which an unwanted nonselective heating of both cancerous as well as healthy tissue may occur, as suggested by Hergt.\u003c/p\u003e\u003c/div\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eIn conclusion, different divalent metal-doped (Ni\u003csup\u003e2+\u003c/sup\u003e, Co\u003csup\u003e2+\u003c/sup\u003e, Zn\u003csup\u003e2+\u003c/sup\u003e, and Mn\u003csup\u003e2+\u003c/sup\u003e) MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e NPs with noticeable aqueous stability, small sizes, ferromagnetic behavior, and excellent heating efficiencies were constructed. The magneto-thermal abilities of the MNPs were investigated as function of concentration of MNPs, field amplitude, and frequency. It was found that Ni-doped ferrite NPs showed the highest heating capabilities reaching hyperthermia temperatures (42\u0026deg;C) very fast in ~\u0026thinsp;5 min with SAR\u0026thinsp;=\u0026thinsp;54.74 W/g, where temperatures up to 55\u0026deg;C can be reached. The good heating efficiencies, high SAR values, and low toxicities of the doped MNPs, particularly for Ni and Co-doped magnetite NPs, strongly suggest their promising potential for magnetic hyperthermia applications.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that supports the findings reported herein are available upon request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the continuous financial support of the College of Science at University of Bahrain. The authors would like to thank Dr. Dalaver Anjum for conducting the STEM-EELS at Khalifa University of Science and Technology. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eK.H.B. conceived and designed the study. K.H.B. prepared all the samples. O.M.L. performed the characterization and magnetization of the samples. S.A. conducted the magnetic hyperthermia measurements and calculated SAR and ILP values. B.A. performed XRD and Rietveld analysis. R.A. performed MTT cell viability experiments. N.M. conducted magnetic parameters and fittings. K.H.B. analyzed the experimental data and wrote the manuscript. O.M.L. helped with the manuscript preparation and discussing the magnetization results. All authors reviewed and approved the manuscript.\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAdditional Information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSupplementary information\u0026nbsp;\u003c/strong\u003eaccompanies this paper at http://www.nature.com/scientificreoprts \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare no competing financial and/or non-financial interests in relation to the work described.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWu, W., Jiang, C. Z. \u0026amp; Roy, V. A. L. 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Phys. \u003c/em\u003e\u003cstrong\u003e19\u003c/strong\u003e, 8363-8372, doi:10.1039/C6CP08743D (2017).\u003c/li\u003e\n\u003cli\u003eAli, R.\u003cem\u003e et al.\u003c/em\u003e Isolation and characterization of a new naturally immortalized human breast carcinoma cell line, KAIMRC1. \u003cem\u003eBMC Cancer\u003c/em\u003e \u003cstrong\u003e17\u003c/strong\u003e, 803, doi:10.1186/s12885-017-3812-5 (2017).\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Magnetic hyperthermia, iron oxide nanoparticles, magnetite, doped iron oxides, doped ferrites, SAR, ILP","lastPublishedDoi":"10.21203/rs.3.rs-3872967/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3872967/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThere is an incessant demand to keep improving on the heating responses of polymeric magnetic nanoparticles (MNPs) under magnetic excitation, particularly in their pursuit to be utilized for clinical hyperthermia applications. Herein, we report the fabrication of a panel of PVP-coated metal-doped MFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e (M\u0026thinsp;\u0026cong;\u0026thinsp;Co, Ni, Mn, Zn) MNPs prepared \u003cem\u003evia\u003c/em\u003e the \u003cem\u003eKo-precipitation Hydrolytic Basic\u003c/em\u003e (KHB) methodology and assess their magnetic and self-heating abilities. The physiochemical, structural, morphological, compositional, and magnetic properties of the doped MNPs were fully characterized using various spectroscopic techniques mainly TEM, XRD, FTIR, and VSM. The obtained MNPs exhibited stabilized quasi-spherical sized particles (10\u0026ndash;15 nm), well-crystallized cubic inverse spinel phases, high saturation magnetizations (26\u0026ndash;81 emu/g) and ferromagnetic behavior. In response to alternating magnetic field (AMF), distinctive heating responses of these doped ferrite NPs were attained. Heating efficacies and specific absorption rate (SAR) values as functions of concentration, frequency, and amplitude were systematically investigated. The highest heating performance was observed for PVP-NiFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e followed by PVP-CoFe\u003csub\u003e2\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e and the least for PVP-Zn-doped and Mn-doped MNPs (SAR values Ni\u0026thinsp;\u0026gt;\u0026thinsp;Co\u0026thinsp;\u0026gt;\u0026thinsp;Zn\u0026thinsp;\u0026gt;\u0026thinsp;Mn). Finally, cytotoxicity assay was conducted on aqueous dispersions of the doped ferrite NPs, proving their biocompatibility and low toxicity. Our results strongly suggest that the PVPylated metal-doped ferrite NPs prepared here, particularly Ni- and Co-doped MNPs, are promising vehicles for potential combined magnetically-triggered biomedical hyperthermia applications.\u003c/p\u003e","manuscriptTitle":"Assessing heating efficiencies of PVPylated divalent metal-doped MFe2O4 nanoparticles for magnetic hyperthermia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-29 04:22:25","doi":"10.21203/rs.3.rs-3872967/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"38479576-3b81-4f35-889b-25dc266f1b0c","owner":[],"postedDate":"January 29th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":28405965,"name":"Physical sciences/Chemistry"},{"id":28405966,"name":"Physical sciences/Chemistry/Materials chemistry"},{"id":28405967,"name":"Physical sciences/Nanoscience and technology"},{"id":28405968,"name":"Physical sciences/Nanoscience and technology/Nanoscale materials"},{"id":28405969,"name":"Physical sciences/Materials science"},{"id":28405970,"name":"Physical sciences/Materials science/Nanoscale materials"}],"tags":[],"updatedAt":"2024-02-10T09:59:14+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-29 04:22:25","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3872967","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3872967","identity":"rs-3872967","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}