Optimisation of aqueous synthesis of iron oxide nanoparticles for biomedical applications

Iron oxide nanoparticles (IONPs) were prepared via aqueous synthesis which combines alkaline co-precipitation (CP) of ferric and ferrous precursors with mild hydrothermal (HT) treatment without cupping agents (CA). In this novel synthesis route, CP + HT, we found the optimal synthesis conditions to obtain IONPs without a second phase and with the size larger than in standard CP: the equal number of Fe(II) and Fe(III) ions are co-precipitated with 6 M ammonia and further HT treated in mild conditions (120 degrees C for 24 h) without CA. The IONPs obtained by novel CP + HT route had faceted rectangular morphology, a mean TEM diameter of 21.5 +/- 6.3 nm, a hydrodynamic diameter of 30.2 +/- 9.1 nm and a zeta potential at pH 4 of 48.2 +/- 0.6 mV. After the subsequent oxidation step, the final product (IONPs) was studied by XRD, FTIR and XPS, which confirmed the desired structure of gamma-Fe2O3. Importantly, this synthesis was especially planned for the preparation of IONPs for biomedical applications. Thus, our novel synthesis was designed to be compliant with the regulations of nano-safety: no special atmosphere, no complex multistep size separation, no organic solvents or solvent exchange, no CA and their washing and the use of low temperature in the final optimised conditions. In addition, this simple synthesis route combines the CP and HT methods, which are both proven to be scalable. Moreover, repeatability and reproducibility of the optimal CP + HT synthesis were confirmed on the lab-scale; more than 100 repetitions with different dishes, different operators and different batches of chemicals were performed.