FROP-1 peptide-conjugated ultrasmall superparamagnetic nanoparticles as a targeted T1-weighted MR contrast agent for...

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 Fe₃O₄ NPs were conjugated with the FROP-1 peptide by 1-ethyl-3-(3-dimethylaminopropyl) carbide diamide hydrochloride (EDC) to form a novel Fe₃O₄@FROP-1 specific target contrast agent. The specificity and targeting of Fe₃O₄@FROP-1 to bind FROP-1 receptors were investigated in vitro by cellular uptake and cellular MR imaging.

In this study, the synthesis of water-soluble ultrasmall Fe₃O₄ NPs was performed by the co-precipitation method. XRD, TEM, and VSM analyses showed the formation of the Fe₃O₄ 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 Fe₃O₄ NPs. The synthesized Fe₃O₄@FROP-1 NPs showed good biocompatibility, and the high r1 relaxivity and r2/r1, respectively, were 2.608 mM^- 1S^- 1 and 1.18. The biocompatibility of the Fe₃O₄ and Fe₃O₄@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.

It was found that the contrast intensity of the Fe₃O₄@FROP-1 nanoprobe increases as Fe concentration increases. Cellular uptake of the Fe₃O₄ and Fe₃O₄@FROP-1 NPs was quantified using ICP-MS. The synthesized NPs had better imaging performance than Dotarem (gadoterate meglumine). The findings showed that Fe₃O₄@FROP-1 NPs have potential utility as a specific and targeted T1-weighted contrast agent in breast cancer MR imaging.