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

Abstract

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 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.

Ultra-small manganese dioxide nanoparticles with high T1 relaxivity for magnetic resonance angiography

“…(2) The abundant carboxyl groups on the surface of the MnO 2 /PAA200 NPs might contribute to better water dispersibility, which allowed more water molecules existing around the nanoparticles to coordinate with the surface-exposed manganese, leading to relaxivity enhancement. 42 (3) The longitudinal relaxivity ( r 1 ) is not only determined by the size-dependent surface-to-volume ratio, but also related to the stability of the nanoparticles. Reduction of the nanoparticle size significantly increases the surface energy, 43 which leads to further decreases in the stability and r 1 .…”

Kilogram‐Scale Synthesis of Extremely Small Gadolinium Oxide Nanoparticles as a T1‐Weighted Contrast Agent for Magnetic Resonance Imaging

“…In addition, small hydrodynamic diameter (<6 nm) is conducive to ensure that nanoparticles can be rapidly excreted from human body through renal excretion. [ 16 ] The small hydrodynamic diameter and good dispersibility of ES‐GdON‐PMA‐9 can markedly reduce its blood circulation half‐life and the risk of Gd deposition compared to other GdONs.…”

Recent trends in preparation and biomedical applications of iron oxide nanoparticles

“…Exceedingly small IONPs were synthesized, and showed non-toxicity in human breast cancer cells. The synthetic IONPs exhibited enhanced MRI capability comparable to commercial contrast agents [ 98 ]. The cell viability of 4T1 cells were 48.5% after treated with ellipsoidal IONPs (100 μg Fe/mL) under an AMF [ 99 ].…”