title: Targeted gene silencing using a follicle-stimulating hormone peptide-conjugated nanoparticle system improves its specificity and efficacy in ovarian clear cell carcinoma in vitro.
abstract: BACKGROUND
  RNA interference technology has shown high therapeutic potential for cancer treatment. However, serum instability, poor tissue permeability and non-specific uptake of short interfering RNA (siRNA) limit its administration in vivo. To overcome these limitations and improve the specificity for ovarian cancer, we developed a targeted nanoparticle delivery system for siRNA. This system included follicle-stimulating hormone (FSH) β 33-53 peptide as a targeting moiety that specifically recognized FSH receptor (FSHR) expressed on ovarian cancer cells. Growth regulated oncogene α (gro-α) has been reported to be involved in ovarian cancer development and progression. Thus, siRNA targeted to gro-α was used as an antitumor drug in this delivery system.
  
  
  METHODS
  FSH β 33-53 peptide-conjugated gro-α siRNA-loaded polyethylene glycol (PEG)-polyethylenimine (PEI) nanoparticles (FSH33-G-NP) were prepared and characterized by gel retardation assay and transmission electron microscopy. Particle size and zeta potential were determined. Expression of gro-α mRNA and protein was detected by real-time quantitative RT-PCR, immunocytochemistry and enzyme-linked immunosorbent assay. The proliferation, migration and invasion of the ovarian clear cell carcinoma cell line ES-2 were evaluated by cell counting kit-8 assay, cell scratch assay and transwell migration assay.
  
  
  RESULTS
  A siRNA sequence that is effective in silencing gro-α expression was obtained and loaded into the targeted delivery system. Compared with gro-α siRNA-loaded nanoparticles without FSH peptide modification (G-NP), FSH33-G-NP significantly down-regulated gro-α expression in ES-2 cells at mRNA and protein levels. Consequently, the aggressive biological behaviors of ES-2 cells, including proliferation, migration and invasion, were suppressed after silencing gro-α expression, and the addition of the FSH β 33-53 peptide enhanced the suppressive effects.
  
  
  CONCLUSIONS
  This study indicated that a FSHR-mediated delivery system could mediate the highly selective delivery of siRNA into ovarian cancer cells and that silencing gro-α expression could be a potential choice for ovarian cancer treatment.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Hong
authors.affiliation: Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, People's Republic of China. xyzhang80@gmail.com.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Jiabing
authors.initials: J
authors.lastname: Zhou
authors.forename: Yufang
authors.initials: Y
authors.lastname: Zheng
authors.forename: Congjian
authors.initials: C
authors.lastname: Xu