Influence of coprecipitation synthesis parameters on the physicochemical properties and biological effects of iron oxide nanoparticles

Iron oxide nanoparticles (IONPs) are promising candidates for a variety of biomedical applications thanks to their magnetic properties and biocompatibility. However, optimising their physicochemical and biological behaviour through fine-tuning their synthesis remains challenging. In this study, we systematically investigated the effect of variations in coprecipitation synthesis parameters, including Fe²⁺/Fe³⁺ ratios, NaOH concentration, stirring speed, temperature and dosing rate, on IONP size, cytotoxicity and blood coagulation. Our robust regression model (<i>R</i> ² = 0.91) revealed that the concentration of Fe²⁺ and its interaction with the other synthesis factors had a strong influence on particle size, which ranged from 3 to 16 nm while maintaining the magnetite phase. All synthesised nanoparticles demonstrated excellent biocompatibility, with no evidence of cytotoxicity observed. Notably, all IONPs induced a significant reduction in coagulation time (CT), indicating a procoagulant effect modulated by synthesis conditions: higher Fe³⁺ values prolonged CT, whereas increased Fe²⁺ values accelerated clotting. Particle size predominantly influenced clot formation time (CFT) and clot firmness without compromising final clot stability, suggesting nuanced modulation of haemostasis. These findings emphasise the critical role of nanoparticle surface chemistry and synthesis control in tailoring IONP properties for biomedical applications.