Continuous synthesis of extremely small-sized iron oxide nanoparticles used for T1-weighted magnetic resonance imaging viaa fluidic reactor

Extremely small-sized iron oxide nanoparticles (ESIONPs) with sizes less than 5 nm have shown great promise as T1contrast agents for magnetic resonance imaging (MRI). However, their facile and scalable production with simultaneously endowed biocompatible surface chemistry remains difficult to be realized. In this study, by using the coprecipitation method implemented in a specially designed gas/liquid mixed phase fluidic reactor, polyglucose sorbitol carboxymethyether (PSC) coated ESIONPs were continuously synthesized with controllable particle sizes ranging from 1.8 to 4 nm. Among the differently sized ESIONPs, the 3.7-nm ESIONPs exhibit the best performance as T1MRI contrast agent, featuring a high r1value of 4.11 (mmol L−1)−1s−1and low r2/r1ratio of 7.90 under a clinical 3 T MR scanning, as well as the excellent T1MRI contrast effect in not only water but also the cellular environment and blood vessel. Furthermore, the ESIONPs possess long-term stability and good dispersity in aqueous dispersions, making them ideal candidates as safe and effective T1-weighted MRI contrast agent for real clinical use.