Oil-in-water microemulsion procedure for coating ferromagnetic Zn ferrite clusters in a SiO2 layer : The magnetostatic interactions between magnetic NPs depend on the distances between them, therefore these interactions can be reduced or canceled by coating NPs with a non-magnetic layer. Silicon oxide (SiO2) is a reliable option because it has a number of properties suitable for bio-medical applications: it is transparent in the infrared zone, it is biocompatible, it can chemically bind various therapeutic molecules by light procedures, etc. It should also be considered that the use of magnetic NPs coated with a layer of SiO2 in in vivo studies, and later in clinical trials, requires quantities of tens of grams, the preparation of which can take, by current methods of preparation, even weeks / whole months, depending on the synthesis capacity of the laboratory. Therefore, the elaboration of a process by which the coating of any type of magnetic NPs to be achieved as quickly and efficiently as possible is a major desideratum in this field. Moreover, in the case of ferromagnetic NPs, the encapsulation process must inhibit the formation of large (micrometric) aggregates before the growth of the SiO2 shell around the pre-existing clusters following the synthesis methods.

Within this project we developed a new method of SiO2 coating of ferromagnetic NPs. Compared to classic methods based on the Stober process or water-in-oil microemulsion, our method is fast, easy, efficient and environmentally friendly at the same time. The method of encapsulation with SiO2 layer consists in the use of an oil-in-water microemulsion, obtained by dispersing the internal phase (dispersion of NPs in hexane and SiO2 precursors) in the external phase (aqueous ammonia solution) using a surfactant (TWEEN 20 or TWEEN 80), which is then subjected to ultrasound for 30 minutes (Fig. 2a-d). The droplets, which confine hydrophobic NPs dispersed in hexane, by ultrasonication become very small and disperse in the entire volume of the external phase, practically inhibiting the agglomeration of NPs in micrometric aggregates (Fig. 2e). Thus, by rapid hydrolysis of tetraethyl orthosilicate at the interface of the two phases under the action of ammonia-generated hydroxide ions, around the nanometric clusters of NPs contained in droplets, a layer of SiO2 is formed consistent and visible in the TEM image (Fig. 2f). Cytotoxicity studies performed on two cell lines - one normal and one cancerous - by two complementary cytotoxicity tests (Alamar Blue and Netral Red) revealed a threshold concentration of 250 μg / cm2 (0.8 mg / mL) of in which SiO2 coated Zn ferrites produce intrinsic toxicity. Compared to uncoatedZn ferrites, they have a three times higher rate of cell internalization. For these reasons, SiO2 coated Zn ferrites are very effective in destroying cancer cells as heating agents. In vitro magnetic hyperthermia experiments have shown that they can induce the death of cancer cells starting at a concentration of 31.25 μg / cm2 (0.1 mg / mL) at an alternating magnetic field strength and frequency of 20 kA / m and respectively 355 kHz (Fig. 2g).