FROP-1 peptide-conjugated ultrasmall superparamagnetic nanoparticles as a targeted T1-weighted MR contrast agent for breast cancer: in vitro study.

BACKGROUND

The aim of this study was to produce ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (NPs) conjugated to the FROP-1 peptide for targeted magnetic resonance imaging (MRI) of breast cancer cell lines and to evaluate its application as a specific and targeted T1-weighted MR imaging contrast agent in vitro. Sodium citrate-stabilized FeO NPs were conjugated with the FROP-1 peptide by 1-ethyl-3-(3-dimethylaminopropyl) carbide diamide hydrochloride (EDC) to form a novel FeO@FROP-1 specific target contrast agent. The specificity and targeting of FeO@FROP-1 to bind FROP-1 receptors were investigated in vitro by cellular uptake and cellular MR imaging.

RESULTS

In this study, the synthesis of water-soluble ultrasmall FeO NPs was performed by the co-precipitation method. XRD, TEM, and VSM analyses showed the formation of the FeO NPs with an average size of about 3.78 ± 0.2 nm. FT-IR spectroscopy approved the conjugation of the FROP-1 peptide with the FeO NPs. The synthesized FeO@FROP-1 NPs showed good biocompatibility, and the high r1 relaxivity and r2/r1, respectively, were 2.608 mMS and 1.18. The biocompatibility of the FeO and FeO@FROP-1 NPs on the MCF-7, SKBR-3, MDA-MB-231, and MCF-10 cell lines was determined using cytotoxicity analysis. The specific targeting effect on the cells was verified by in vitro cellular uptake and cell MR imaging.

CONCLUSION

It was found that the contrast intensity of the FeO@FROP-1 nanoprobe increases as Fe concentration increases. Cellular uptake of the FeO and FeO@FROP-1 NPs was quantified using ICP-MS. The synthesized NPs had better imaging performance than Dotarem (gadoterate meglumine). The findings showed that FeO@FROP-1 NPs have potential utility as a specific and targeted T1-weighted contrast agent in breast cancer MR imaging.