title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Radiology, Obstetrics and Gynecology Hospital, Fudan University, No.419 Fangxie Road, Shanghai, 200011, P. R. China.
authors.forename: He
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, P. R. China.
authors.forename: Jingchao
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, P. R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, P. R. China.
authors.forename: Mingwu
authors.initials: M
authors.lastname: Shen
authors.affiliation: College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai, 201620, P. R. China. xshi@dhu.edu.cn.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Shi
authors.affiliation: Department of Radiology, Obstetrics and Gynecology Hospital, Fudan University, No.419 Fangxie Road, Shanghai, 200011, P. R. China. zhangguofu1018@163.com.
authors.forename: Guofu
authors.initials: G
authors.lastname: Zhang
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage; D055088:Early Detection of Cancer; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000008:administration & dosage; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000175:diagnosis*
chemical_list: D003287:Contrast Media; D058185:Magnetite Nanoparticles; D005492:Folic Acid
keywords: Folic acid; Iron oxide nanoparticles; Magnetic resonance imaging; Ovarian cancer; Targeting