Hyper-Cube project aimed at scaling up the synthesis procedure of iron oxide nanocubes (IONCs) and to find a scalable protocol for the surface functionalization of nanocubes with a thermo-responsive (TR) polymer. These scale-up protocols are required to allow an effective translation of these materials (IONCs and TR-cubes) from the laboratory production to their commercialization and to their future application for clinical purposes. In particular, IONCs and TR-IONCs are primarily designed to be used as heat mediators in magnetic hyperthermia (MH) while the TR-cubes can also serve as drug carrier agents for the deliverable of chemotherapeutic drugs in a heat-controlled manner to achieve a localized and targeted chemotherapy for the treatment of tumors. Following the objectives of this project, we have succeeded in scaling up the synthesis of the IONCs. We now have a robust and reproducible procedure that enables the production, at gram scale, of magnetic material while possessing outstanding structural and magnetic properties. With our solvothermal method, we produce up to 8 g of the total mass of magnetic material in a single thermalization cycle (3h), when using multiple autoclaves in parallel per oven. Moreover, we are able to tune the size of the nanocubes between 8 and 40 nm. The obtained IONCs reach specific adsorption rate (SAR) values (the heat rate at which magnetic materials absorbed electromagnetic energy and convert to heat), which are comparable to the best nanocubes obtained by thermal decomposition methods but, in this case, produced in milligram amounts. Finally, by choosing some alternative shape directing molecules we have managed to set protocols for obtaining nanoparticle of shapes different from the nanocubes but still having a high shape anisotropy. Among them, we have produced faceted nanoparticles and concave nanocubes (star-like shape) which showed outstanding heating properties and, at some magnetic field conditions, have SAR values even higher than cubic-shape nanoparticles. The second objective aimed at the scale-up production of TR-IONCs for MH therapy and pharmaceutical purposes. To this aim, we have implemented in our lab. a novel apparatus for the in-flow production of the TR-IONCs. Different from previous in-batch (flask) synthesis approach with this new protocol, the TR-cubes obtained do not suffer from batch-to-batch variabilities, low material recovering, and long reaction time.
