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Targeted paclitaxel nanoparticles modified with follicle-stimulating hormone β 81–95 peptide show effective antitumor activity against ovarian carcinoma

Authors
Journal
International Journal of Pharmaceutics
0378-5173
Publisher
Elsevier
Publication Date
Volume
453
Issue
2
Identifiers
DOI: 10.1016/j.ijpharm.2013.06.038
Keywords
  • Ovarian Carcinoma
  • Targeted Therapy
  • Follicle Stimulating Hormone
  • Paclitaxel
  • Nanoparticle
Disciplines
  • Medicine

Abstract

Abstract The majority of patients with advanced ovarian cancer will experience a relapse and ultimately die from refractory diseases. Targeted therapy shows promise for these patients. Novel therapeutic strategies should be developed on the basis of the molecular mechanisms involved in ovarian cancer and the steroid hormone environment of ovaries. The ovary is the main target organ of follicle-stimulating hormone (FSH), which bind to its receptor with high affinity. In this study a FSH receptor-targeting ligand, FSH β 81–95 peptide, was used as a targeting moiety to synthesize an FSH receptor-mediated drug delivery system. FSH β 81–95 peptide-conjugated nanoparticles (FSH81-NPs) and paclitaxel-loaded FSH81-NPs (FSH81-NP-PTXs) were synthesized. In vitro studies showed that FSH β 81–95 peptide enabled the specific uptake of cytotoxic drugs and increased the intracellular paclitaxel concentration in FSH receptor-expressing cancer cells, resulting in enhanced cytotoxic effects. In vivo studies showed that FSH81-NP-PTXs possessed higher antitumor efficacy against FSH receptor-expressing tumors without any clinical signs of adverse side effects or body weight loss due to modification with FSH β 81–95 peptide. Therefore, FSH binding peptide-targeted drug delivery system exhibited high potential in the treatment of ovarian cancer, and tumor targeting via reproductive hormone receptors might improve the outcome of diseases.

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