In vitro and in vivo evaluation of folate receptor-targeted a novel magnetic drug delivery system for ovarian cancer therapy


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Ak G. , Yılmaz H., Güneş A., Sanlier Ş.

ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY, vol.46, 2018 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 46
  • Publication Date: 2018
  • Doi Number: 10.1080/21691401.2018.1439838
  • Title of Journal : ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY
  • Keywords: Ovarian cancer, targeted drug delivery, folate receptor, magnetic nanoparticles, doxorubicin, erythrocyte vesicle, COATED MAGNETITE, NANOPARTICLES, DOXORUBICIN, FUNCTIONALIZATION, BIODISTRIBUTION, NANOCARRIERS, RESISTANCE, STABILITY, MICELLES, DESIGN

Abstract

Doxorubicin is widely used anticancer drug; however, use of doxorubicin is limited. Under externally applied magnetic field, magnetic agents can help to transport drug directly to tumor. Folate receptor is overexpressed in ovarian carcinomas. In this study, we aimed to develop magnetically responsive and folate receptor-targeted biomimetic drug delivery system for ovarian cancer therapy. Doxorubicin-loaded and glucose/gluconic acid-coated magnetic nanoparticles were synthesized and erythrocyte membrane vesicles were used for coating of nanoparticles. Folate ligand was anchored to surface so as to target receptor. Hydrodynamic size of nanocarrier was found as 91.2 +/- 20.8nm. The results showed that delivery system has controlled drug release profile and biocompatible features. In folate-free medium, folate receptor-targeted nanocarrier showed 10.33-fold lower IC50 values for A2780 cells and 3.93-fold lower for OVCAR3 cells compared to non-targeted nanoparticles and demonstrated more cytotoxicity against ovarian cancer cells. Moreover, magnetically and folate receptor-targeted doxorubicin delivery system was significantly more effective for therapy of xenografted nude mice than free doxorubicin based on tumor shrinkages and biochemical parameters. In conclusion, it can be suggested that folate ligand-attached and biomimetically designed magnetic drug delivery system have advantages and potential for targeted ovarian cancer therapy.