Moderate cooling coprecipitation for extremely small iron oxide as pH dependent T1-MRI contrast agent
Iron based nanomedicine (IBNM) has been one powerful diagnostic tool as magnetic resonance imaging (MRI) contrast agent (CA) in clinic for years. Conventional IBNMs are generally employed as T2-MRI CA, but most of them are constrained in clinical indication expansion by magnetic susceptibility artifact. In comparison, extremely small iron oxide (ESIO) with core size less than 5 nm has demonstrated T1-MRI effect, which provides prospect for the Gd-based agent alternative. Nevertheless, current developed ESIOs for T1-MRI CA always require harsh conditions such as high temperature and high boiling reagent. Moreover, very few of currently developed ESIOs meet the stringent pharmaceutical standard. Herein, on basis of crystal nuclear precipitation-dissolution equilibrium mechanism and outer/inner sphere T1-MRI theory, monodisperse ESIOs with average size of 3.43 nm (Polydispersity Index 0.104) are fabricated using moderate cooling procedure with mild coprecipitation reaction condition. The as-synthesized ESIOs display around 3-fold T1 MRI signal intensity higher than that of commercial Ferumoxytol (FMT), comparable to that of Gd-based CA in vitro. Additionally, the T1-MRI performance of the ESIOs is pH dependent and delivers bright signal augmentation. Eventually, the internalization into mesenchyma stem cell based on ESIO is realized in the absence of transferring agent. Considering the identical structure and composition of ESIOs as those of FMT, they could meet the pharmaceutical criteria, thus providing great potential as T1-MRI CA for instance stem cell tracer.