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 Fe ₃O ₄ NPs were prepared.

Results

FA-targeted Fe ₃O ₄ 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 Fe ₃O ₄ NPs have a targeting specificity to Skov-3 cells overexpressing FA receptors. FA-targeted Fe ₃O ₄ 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 T ₂ signal intensities of xenograft tumor tissues when injected with FA-targeted and non-targeted Fe ₃O ₄ NPs at 4 h post-injection.

Conclusion

FA-targeted Fe ₃O ₄ 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.