Biodegradable and biocompatible exceedingly small magnetic iron oxide nanoparticles for T1-weighted magnetic resonance imaging of tumors

• DOI: 10.1186/s12951-022-01562-y
• Publication Date: 2022-07-30T07:02:55Z
• Authors: Xuanyi Lu; Huimin Zhou; Zhiyu Liang; Jie Feng; Yudie Lu; Lin Huang; Xiaozhong Qiu; Yikai Xu; Zheyu Shen
• Keywords: Contrast agents (CAs); Research; Contrast Media; Water; Magnetic Resonance Imaging; 01 natural sciences; 0104 chemical sciences; Mice; Exceedingly small magnetic iron oxide nanoparticles (ES-MIONs); Neoplasms; Poly (aspartic acid) (PASP); Medical technology; Biodegradable; Animals; Magnetic Iron Oxide Nanoparticles; Tissue Distribution; Magnetic resonance imaging (MRI); R855-855.5; TP248.13-248.65; Biotechnology

AbstractMagnetic 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 T1 CAs, commercial magnetic iron oxide nanoparticles (MIONs)-based T2 CAs, and reported exceedingly small MIONs (ES-MIONs)-based T1 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 T1-weighted MRI of tumors. After optimization of the synthesis conditions, the final obtained ES-MION9 with 3.7 nm of diameter has a high r1 value (7.0 ± 0.4 mM−1 s−1) and a low r2/r1 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. T1-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 T1-weighted CAs with promising translational possibility to compete with the commercial Gd chelates.