Zn doped iron oxide nanoparticles with high magnetization and photothermal efficiency for cancer treatment.

Magnetic nanoparticles (NPs) are powerful agents to induce hyperthermia in tumours upon the application of an alternating magnetic field or an infrared laser. Dopants have been investigated to alter different properties of materials. Herein, the effect of zinc doping into iron oxide NPs on their magnetic properties and structural characteristics has been investigated in-depth. A high temperature reaction with autogenous pressure was used to prepare iron oxide and zinc ferrite NPs of same size and morphology for direct comparison. Pressure was key in obtaining high quality nanocrystals with reduced lattice strain (27% less) and enhanced magnetic properties. Zn0.4Fe2.6O4 NPs with small size of 10.2 ± 2.5 nm and very high saturation magnetisation of 142 ± 9 emu gFe+Zn-1 were obtained. Aqueous dispersion of the NPs showed long term magnetic (up to 24 months) and colloidal stability (at least 6 d) at physiologically mimicking conditions. The samples had been kept in the fridge and had been stable for four years. The biocompatibility of Zn0.4Fe2.6O4 NPs was next evaluated by metabolic activity, membrane integrity and clonogenic assays, which show an equivalence to that of iron oxide NPs. Zinc doping decreased the bandgap of the material by 22% making it a more efficient photothermal agent than iron oxide-based ones. Semiconductor photo-hyperthermia was shown to outperform magneto-hyperthermia in cancer cells, reaching the same temperature 17 times faster whilst using 20 times less material (20 mgFe+Zn ml-1vs. 1 mgFe+Zn ml-1). Magnetothermal conversion was minimally hindered in the cellular confinement whilst photothermal efficiency remained unchanged. Photothermia treatment alone achieved 100% cell death after 10 min of treatment compared to only 30% cell death achieved with magnetothermia at clinically relevant settings for each at their best performing concentration. Altogether, these results suggest that the biocompatible and superparamagnetic zinc ferrite NPs could be a next biomaterial of choice for photo-hyperthermia, which could outperform current iron oxide NPs for magnetic hyperthermia.

TRAIL acts synergistically with iron oxide nanocluster-mediated magneto- and photothermia.

Targeting TRAIL (Tumor necrosis factor (TNF)-Related Apoptosis-Inducing Ligand) receptors for cancer therapy remains challenging due to tumor cell resistance and poor preparations of TRAIL or its derivatives. Herein, to optimize its therapeutic use, TRAIL was grafted onto iron oxide nanoclusters (NCs) with the aim of increasing its pro-apoptotic potential through nanoparticle-mediated magnetic hyperthermia (MHT) or photothermia (PT). Methods: The nanovector, NC@TRAIL, was characterized in terms of size, grafting efficiency, and potential for MHT and PT. The therapeutic function was assessed on a TRAIL-resistant breast cancer cell line, MDA-MB-231, wild type (WT) or TRAIL-receptor-deficient (DKO), by combining complementary methylene blue assay and flow cytometry detection of apoptosis and necrosis. Results: Combined with MHT or PT under conditions of "moderate hyperthermia" at low concentrations, NC@TRAIL acts synergistically with the TRAIL receptor to increase the cell death rate beyond what can be explained by the mere global elevation of temperature. In contrast, all results are consistent with the idea that there are hotspots, close to the nanovector and, therefore, to the membrane receptor, which cause disruption of the cell membrane. Furthermore, nanovectors targeting other membrane receptors, unrelated to the TNF superfamily, were also found to cause tumor cell damage upon PT. Indeed, functionalization of NCs by transferrin (NC@Tf) or human serum albumin (NC@HSA) induces tumor cell killing when combined with PT, albeit less efficiently than NC@TRAIL. Conclusions: Given that magnetic nanoparticles can easily be functionalized with molecules or proteins recognizing membrane receptors, these results should pave the way to original remote-controlled antitumoral targeted thermal therapies.