Biodegradable and biocompatible exceedingly small magnetic iron oxide nanoparticles for T 1 -weighted magnetic resonance imaging of tumors

Magnetic resonance imaging (MRI) has been widely using in clinical diagnosis, and contrast agents (CAs) can improve the sensitivity MRI. To overcome the problems of commercial Gd chelates-based T 1 CAs, commercial magnetic iron oxide nanoparticles (MIONs)-based T 2 CAs, and reported exceedingly small MIONs (ES-MIONs)-based T 1 CAs, in this study, a facile co-precipitation method was developed to synthesize biodegradable and biocompatible ES-MIONs with excellent water-dispersibility using poly (aspartic acid) (PASP) as a stabilizer for T 1 -weighted MRI of tumors. After optimization of the synthesis conditions, the final obtained ES-MION9 with 3.7 nm of diameter has a high r 1 value (7.0 ± 0.4 mM −1 s −1 ) and a low r 2 / r 1 ratio (4.9 ± 0.6) at 3.0 T. The ES-MION9 has excellent water dispersibility because of the excessive –COOH from the stabilizer PASP. The pharmacokinetics and biodistribution of ES-MION9 in vivo demonstrate the better tumor targetability and MRI time window of ES-MION9 than commercial Gd chelates. T 1 -weighted MR images of aqueous solutions, cells and tumor-bearing mice at 3.0 T or 7.0 T demonstrate that our ES-MION9 has a stronger capability of enhancing the MRI contrast comparing with the commercial Gd chelates. The MTT assay, live/dead staining of cells, and H&E-staining indicate the non-toxicity and biosafety of our ES-MION9. Consequently, the biodegradable and biocompatible ES-MION9 with excellent water-dispersibility is an ideal T 1 -weighted CAs with promising translational possibility to compete with the commercial Gd chelates.