Preparation, biocompatibility and imaging performance of ultrasmall iron oxide magnetic fluids for T1/T2-weighted MRI

Abstract

In order to further improve the stability and biocompatibility of magnetic fluids (MFs), we report a one-step protocol for the preparation of ultrasmall superparamagnetic iron oxide MFs. Four kinds of MFs (n %L-Cysteine-S-branched polymethacrylic acid-coated Fe3O4 nanoparticles MFs, n %Cys-PMAA@Fe3O4 MFs) with ultrasmall particle size (< 5 nm) were obtained using the different molecular weight of polymer ligands as the outer layer. Among them, 2 %Cys-PMAA@Fe3O4 MFs show the best performance in the apparent particle size (4.10 ± 0.90 nm), hydrodynamic size (< 50 nm), and magnetic weight gain (67 mg), and stability index (I = 99 %). In addition, 2 %Cys-PMAA@Fe3O4 MFs exhibit excellent stability for 180 days under different salt concentrations (up to 3 mol/L) and pH (2−12). Importantly, the 2 %Cys-PMAA@Fe3O4 MFs show good biocompatibility in vitro that HEK293T and MCF-7 cells viability are higher than 90 % in 24 h when the iron concentration is 250 μg·mL−1. Furthermore, the hemolysis test and H&E tissue section staining demonstrate that the MFs are non-toxic in vivo. Finally, the value of 2 %Cys-PMAA@Fe3O4 MFs at 1.5 T (r2 = 57.48 mM−1·s−1, r1 = 8.61 mM−1·s−1, r2/r1 = 6.68) is slightly less than Combidex for r2 (r2 = 65 mM−1·s−1), and 2.5-folds higher than Gd-DTPA for r1 (r1 = 3.5 mM−1·s−1), so the tumor area can be clearly observed with dual-mode imaging at 3.0 T in vivo by the tail vein injection. This study contributes to the rationalized design and development of a clinical dual-modulus contrast agent.