Folic acid-targeted iron oxide nanoparticles as contrast agents for magnetic resonance imaging of human ovarian cancer

Abstract

Background: Improved methods for the early and specific detection of ovarian cancer are needed. Methods: In this experimental study, we used folic acid (FA)-targeted iron oxide (Fe3O4) nanoparticles (NPs) as a T2-negative contrast agent for magnetic resonance (MR) imaging to accurately detect ovarian cancer tissues in an intraperitoneal xenograft tumor model. Human serous ovarian cell line (Skov-3), with overexpressed FA receptors, was chosen as the targeted tumor cell mode. For in vivo experiments, the cells were injected intraperitoneally into nude mice to produce intraabdominal ovarian cancers. FA-targeted and non-targeted Fe3O4 NPs were prepared. Results: FA-targeted Fe3O4 NPs with a mean size of 9.2 ± 1.7 nm have a negligible cytotoxicity to human serous ovarian cell line (Skov-3). Importantly, the results of cellular uptake suggested that FA-targeted Fe3O4 NPs have a targeting specificity to Skov-3 cells overexpressing FA receptors. FA-targeted Fe3O4 NPs could be specifically localized by magnetic resonance (MR) imaging to the intraperitoneal human ovarian carcinoma tissues, as documented by a statistically significant difference (p = 0.002, n = 3) in T2 signal intensities of xenograft tumor tissues when injected with FA-targeted and non-targeted Fe3O4 NPs at 4 h post-injection. Conclusion: FA-targeted Fe3O4 NPs appear to be promising agents for the detection of human ovarian carcinoma by MR imaging, and possibly also for the hyperthermal treatment of the tumors.