Folate-targeted nanoparticle delivery of chemo- and radiotherapeutics for the treatment of ovarian cancer peritoneal metastasis

Michael E. Werner, Shrirang Karve, Rohit Sukumar, Natalie D. Cummings, Jonathan A. Copp, Ronald C. Chen, Tian Zhang, Andrew Z. Wang

Research output: Contribution to journalArticlepeer-review

156 Scopus citations

Abstract

Peritoneal metastasis is a major cause of morbidity and mortality in ovarian cancer. While intraperitoneal chemotherapy and radiotherapy have shown favorable clinical results, both are limited by their non-targeted nature. We aimed to develop a biologically targeted nanoparticle therapeutic for the treatment of ovarian cancer peritoneal metastasis. Folate-targeted nanoparticles encapsulating chemotherapy and/or radiotherapy were engineered. Paclitaxel (Ptxl) was used as the chemotherapeutic and yittrium-90 ( 90Y) was employed as the therapeutic radioisotope. Folate was utilized as the targeting ligand as most ovarian cancers overexpress the folate receptor. Nanoparticle characterization studies showed monodispersed particles with controlled Ptxl release. Folate targeting ligand mediated the uptake of NPs into tumor cells. In vitro efficacy studies demonstrated folate-targeted NPs containing chemoradiotherapy was the most effective therapeutic compared to folate-targeted NPs containing a single therapeutic or any non-targeted NP therapeutics. In vivo efficacy studies using an ovarian peritoneal metastasis model showed that folate-targeted NP therapeutics were significantly more effective than non-targeted NP therapeutics. Among the folate-targeted therapeutics, the NP containing chemoradiotherapy appeared to be the most effective. Our results suggest that folate-targeted nanoparticles containing chemoradiotherapy have the potential as a treatment for ovarian peritoneal metastasis.

Original languageEnglish (US)
Pages (from-to)8548-8554
Number of pages7
JournalBiomaterials
Volume32
Issue number33
DOIs
StatePublished - Nov 2011
Externally publishedYes

Keywords

  • Chemoradiotherapy
  • Chemotherapy
  • Folate-targeted nanoparticles
  • Molecular targeted nanoparticles
  • Nanomedicine
  • Nanoparticle

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Fingerprint

Dive into the research topics of 'Folate-targeted nanoparticle delivery of chemo- and radiotherapeutics for the treatment of ovarian cancer peritoneal metastasis'. Together they form a unique fingerprint.

Cite this