# Magnetic Nanoparticles as Mediators for Magnetic Hyperthermia Therapy Applications: A Status Review
## 2 Syntheses of MNPs  
In our study, we employed four distinct synthesis methods to produce four different types of magnetic nanoparticles (MNPs) specifically designed for applications in MH treatments. For the synthesis of maghemite MNPs, we used FeCl\({}_{2}\cdot\)4H\({}_{2}\)O and FeCl\({}_{3}\cdot\)6H\({}_{2}\)O. The precursors were prepared by the coprecipitation of Fe\({}^{2+}\) and Fe\({}^{3+}\) ions using NH\({}_{4}\)OH and heated to 80 \({}^{\circ}\)C. Then, the CM-dextran solution was added for over 30 min. The suspension was then stored at 80 \({}^{\circ}\)C for 30 min and cooled to room temperature. The suspension was magnetically decanted and washed several times with deionized water [27]. Mg(NO\({}_{3}\))\({}_{2}\cdot\)6H\({}_{2}\)O, Fe(NO\({}_{3}\))\({}_{3}\cdot\)9H\({}_{2}\)O, and Ti(C\({}_{3}\)H\({}_{2}\)O)\({}_{4}\) were used for the synthesis of the Mg\({}_{1+x}\)Fe\({}_{2-2x}\)Ti\({}_{x}\)O\({}_{4}\) complex ferrite. The precursors were prepared by coprecipitation of Fe\({}^{3+}\), Mg\({}^{2+}\), and Ti\({}^{4+}\) ions in different stoichiometric ratios (x = 0.34; 0.37; 0.40) with a NaOH solution (6 M) and heated to 80 \({}^{\circ}\)C. Then, the suspensions were aged at 80 \({}^{\circ}\)C for 1 h. The product was washed several times with deionized water and dried [26]. NiCu MNPs were prepared by reducing a Ni, Cu-hydrazine complex using the microemulsion method [41], via reducing a Ni, Cu-oxide mixture in a silica matrix [50; 103], obtained with a sol-gel method and by mechanical milling [55]. MNPs with a controlled \(T_{\rm C}\) were prepared by reduction of a Ni, Cu-hydrazine complex synthesized in a compartmentalized state of reverse micelles. We used the phase diagram of water/N-cetyl-N,N,N-trimethylammonium bromide (CTAB), and n-butanol/isooctane as a starting point for the preparation of the microemulsion. We used the titration method to select a suitable composition range that would form a microemulsion in the mentioned system. Microemulsion A was prepared with a 0.3 M solution of Ni\({}^{2+}\) and Cu\({}^{2+}\) acidified with HCl and then heated to 60 \({}^{\circ}\)C in a water bath. Microemulsion B was then added to microemulsion A, using hydrazine as the metal-containing ligand. This mixture was heated at 60 \({}^{\circ}\)C for several hours. After the complex was formed, stirring was continued for another hour and NaOH was added. The color change in the microemulsion to a stable black suspension was indicative of the formation of MNPs. The suspension was then centrifuged and washed several times to sediment the particles [41]. MNPs of NiCu alloy with narrow size distribution were prepared by reduction of the Ni and Cu oxide mixture in a silica matrix obtained by the sol-gel method. Ni(NO\({}_{3}\))\({}_{2}\cdot\)6H\({}_{2}\)O, Cu(NO\({}_{3}\))\({}_{2}\cdot\)3H\({}_{2}\)O, and citric acid (CA) were dissolved in deionized water. After 15 min, absolute ethanol and tetraethyl orthosilicate (TEOS) were added to the solution with vigorous stirring. The molar ratio of all components, in the case of the Ni:Cu ratio of 67.5:32.5, was Ni:Cu:CA:TEOS:D.I. :ethanol = 0.675:0.325:1.1:2.9:40.6:11.6. The salt was dried at room temperature for 72 h and then calcined at 500 \({}^{\circ}\)C for 24 h (air atmosphere). We obtained a powder of nickel and copper oxides in a silica matrix, followed by a reduction in an Ar/H\({}_{2}\) atmosphere for one day at 850 \({}^{\circ}\)C. We obtained the final product Ni\({}_{1-x}\)Cu\({}_{x}\) MNPs in a SiO\({}_{2}\) matrix. By etching, the solution was stirred for 1 day under an Ar atmosphere to remove the SiO\({}_{2}\) matrix. The final product was washed several times with etching solution and ethanol and redispersed in ethanol [50]. A series of MNPs from NiCu alloy, which had a \(T_{\rm C}\) in the range of 51 and 63 \({}^{\circ}\)C, was prepared in the following article. Using the sol-gel method, we reduced a mixture of nickel and copper oxides in a silica matrix with some minor modifications [106].