# Application in Nanomedicine of Manganese-Zinc Ferrite Nanoparticles
## 4 In Vivo Applications of Mn-Zn Ferrites
The author hypothesized a model in which the elongated structure has more chance to interact with cellular receptor in the fluid environment, therefore forming the receptor-mediated endocytosis more easily [46]. [PERSON] et al. recently proposed the preparation of small nanoclusters for the therapy of prostatic cancer. Iron oxide nanoparticles doped with zinc and manganese, with a size of 13 nm, were obtained by the thermal decomposition of Fe(acac)\({}_{3}\), ZnCl\({}_{2}\) and MnCl\({}_{2}\). These hydrophobic nanoparticles were subsequently transferred in water using the solvent evaporation method, adding PEG-PCL as template for the preparation of very small clusters of 100 nm. As expected, the doped nanoparticles were characterized by a higher saturation magnetization value (60.33 Am\({}^{2}\)/kg) than iron oxide nanoparticles (57 Am\({}^{2}\)/kg). Moreover, the SAR values (measured in THF at 420 kHz, 26.9 kA/m) were improved for doped nanoparticles (1615.1 W/g) if compared to bare iron oxide nanoparticles (586.2 W/g). When the nanoparticles were clustered and transferred in water, a slight decrease of SAR values was observed, but, regardless, the Mn-Zn magnetic cluster showed a higher performance (1010.0 W/g) than the iron oxide nanoclusters (493.8 W/g). The clusters were intravenously administrated to some nude mice bearing subcutaneous xenografts of DU145 prostate cancer cells. The particles started to accumulate in the tumor site (via passive targeting) after 1 h and reached a maximum concentration after 7 h, with a minor accumulation in other organs (Figure 1A). The application of AFM to the animal induced an intertumoral temperature of 42 \({}^{\circ}\)C and an evident inhibition of the tumor growth, also in comparison to the bare iron oxide clusters (Figure 1B) [47]. [PERSON] et al. started from hydrophobic Mn\({}_{0.6}\)Zn\({}_{0.4}\)Fe\({}_{2}\)O\({}_{4}\) nanoparticles for the preparation of magnetic PEG-\(b\)-PCL block copolymer micelles. The surface of the magnetic cluster was then engineered with hyaluronic acid (HA) for the active targeting of tumor cells, such as A549 (human lung adenocarcinoma cell line), over-expressing the receptor (CD44) for the HA. The purpose of this approach was to combine a magnetic hyperthermia therapeutic approach with radiotherapy for the treatment of non-small-cell lung cancer (Figure 2). By the in vitro test, a synergistic effect of the dual therapy was observed, with a total apoptosis rate of 32.7%, almost four times that of the results of hyperthermia and five times for radiotherapy. The synergistic effect was obtained also by in vivo treatment of xenograft tumor in mice. The nanocomposite was injected by tail vein in the animal and the therapeutic scheme was applied on days 1 and 4. The growth of the tumor appeared to be significantly inhibited with the relative tumor volume ratio shrinking to 49.6% by day 13 in the dual therapy group [48]. Figure 1: (**A**) NIR fluorescence images of a mouse at different time points following intravenous administration of the Mn-Zn magnetic cluster. (**B,C**) Intratumoral temperature curves during AFM and corresponding tumor growth profiles for each experimental group. Adapted with permission from [47], MDPI, 2020. Figure 2: Scheme of the application of the Mn-Zn ferrite nanoclusters in an in vivo AFM experiment. On the left, TEM images of single nanoparticles (bottom) and clustered ones (top). Adapted with permission from [48], Copyright 2020, American Chemical Society.