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.

Quantification of Lipoprotein Uptake in Vivo Using Magnetic Particle Imaging and Spectroscopy.

Lipids are a major source of energy for most tissues, and lipid uptake and storage is therefore crucial for energy homeostasis. So far, quantification of lipid uptake in vivo has primarily relied on radioactive isotope labeling, exposing human subjects or experimental animals to ionizing radiation. Here, we describe the quantification of in vivo uptake of chylomicrons, the primary carriers of dietary lipids, in metabolically active tissues using magnetic particle imaging (MPI) and magnetic particle spectroscopy (MPS). We show that loading artificial chylomicrons (ACM) with iron oxide nanoparticles (IONPs) enables rapid and highly sensitive post hoc detection of lipid uptake in situ using MPS. Importantly, by utilizing highly magnetic Zn-doped iron oxide nanoparticles (ZnMNPs), we generated ACM with MPI tracer properties superseding the current gold-standard, Resovist, enabling quantification of lipid uptake from whole-animal scans. We focused on brown adipose tissue (BAT), which dissipates heat and can consume a large part of nutrient lipids, as a model for tightly regulated and inducible lipid uptake. High BAT activity in humans correlates with leanness and improved cardiometabolic health. However, the lack of nonradioactive imaging techniques is an important hurdle for the development of BAT-centered therapies for metabolic diseases such as obesity and type 2 diabetes. Comparison of MPI measurements with iron quantification by inductively coupled plasma mass spectrometry revealed that MPI rivals the performance of this highly sensitive technique. Our results represent radioactivity-free quantification of lipid uptake in metabolically active tissues such as BAT.

Assessing cell-nanoparticle interactions by high content imaging of biocompatible iron oxide nanoparticles as potential contrast agents for magnetic resonance imaging.

Stem cell tracking in cellular therapy and regenerative medicine is an urgent need, superparamagnetic iron oxide nanoparticles (IONPs) could be used as contrast agents in magnetic resonance imaging (MRI) that allows visualization of the implanted cells ensuring they reach the desired sites in vivo. Herein, we report the study of the interaction of 3,4-dihydroxyhydrocinnamic acid (DHCA) functionalized IONPs that have desirable properties for T2 - weighted MRI, with bone marrow-derived primary human mesenchymal stem cells (hMSCs). Using the multiparametric high-content imaging method, we evaluate cell viability, formation of reactive oxygen species, mitochondrial health, as well as cell morphology and determine that the hMSCs are minimally affected after labelling with IONPs. Their cellular uptake is visualized by transmission electron microscopy (TEM) and Prussian Blue staining, and quantified using an iron specific colourimetric method. In vitro and in vivo studies demonstrate that these IONPs are biocompatible and can produce significant contrast enhancement in T2-weighted MRI. Iron oxide nanoparticles are detected in vivo as hypointense regions in the liver up to two weeks post injection using 9.4 T MRI. These DHCA functionalized IONPs are promising contrast agents for stem cell tracking by T2-weighted MRI as they are biocompatible and show no evidence of cytotoxic effects on hMSCs.