# Application in Nanomedicine of Manganese-Zinc Ferrite Nanoparticles
## 2 Synthetic Strategies of Mn-Zn Ferrites
### Co-Precipitation Method  
The co-precipitation method is one of the most utilized synthesis methods for preparing magnetic nanoparticles [15]. The formation of magnetic nanoparticles is due to the nucleation followed by the crystal growth and there are two steps to follow this precipitation process [16]. The first step is to take account of the solubility for each type of solute and the second step is the addition of an excess of solute, which could result in the precipitation and formation of nanocrystals. For example, for the formation of nanoparticles, the solution has to be in a high state of saturation to start the nucleation. In this case, two kinds of nucleation processes could occur: the heterogeneous nucleation (when nuclei collide and interact with a solid surface) and homogenous nucleation (which takes place in the absence of a solid interface by combining solute molecules to produce nuclei) [17]. Furthermore, for having a uniformity of particle size, it is necessary for distribution to follow a short nucleation period in such a way so as to obtain the uniformity of the nanoparticles without further nucleation. As such, the burst nucleation (induction of a single event) is obtained by increasing the concentration of metal precursors to the critical saturation point. Their magnetization depends on different parameters, like the pH of the suspension, the reaction temperature, and the initial molar concentration [18; 19]. The major drawback of the co-precipitation method is the insufficient size control distribution and the uncontrolled shape, but, nonetheless, this process is a favored route to produce magnetic nanoparticles due to it requiring a low reaction temperature, the high reaction yield and the shorter reaction time than other methods, such as thermal decomposition or hydrothermal synthesis.  
Most of the articles concerning the synthesis of Mn-Zn ferrite NPs exploited the synthesis by co-precipitation. Mainly iron, zinc and manganese chlorides are used [20; 21; 22; 23; 24; 25], but also the respective nitrates [26; 27] and sulfates [28; 29] have been used in various articles. The principle of synthesis is almost always identical and involves the preparation of an aqueous solution of three metal salts and the subsequent addition of a base (mainly NaOH, but also ammonium hydroxide) to induce the co-precipitation of the magnetic nanoparticles. Several studies focused on the analysis of the composition of the nanoparticle, studying the relationship between Mn and Zn in the typical formula Mn(1-x)ZnxFe2O4, related to the typical spinel structure found in this type of nanoparticles. A linear trend was not observed in the literature, as for some studies an increase in the Ms is obtained by increasing the percentage of zinc [20,26], while for others it is the increase of manganese [27,29] that determines a greater Ms. In general, it can be claimed that an equal ratio between the elements (0.5 Mn/0.5 Zn) [24] or a ratio that is slightly shifted towards manganese (0.6-0.8 Mn/0.4-0.2 Zn) [21, 22, 23, 25,29] produces the particles with the best performance in terms of particle size, Ms and heating production by magnetic hyperthermia.