Intraperitoneal nanotherapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin

Canan Schumann, Stephanie Chan, Jess A. Millar, Yuliya Bortnyak, Katherine Carey, Alex Fedchyk, Leon Wong, Tetiana Korzun, Abraham S. Moses, Anna Lorenz, Delany Shea, Olena Taratula, Oleh Khalimonchuk, Oleh Taratula

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Herein, we report an efficient combinatorial therapy for metastatic ovarian cancer based on siRNA-mediated suppression of DJ-1 protein combined with a low dose of cisplatin. DJ-1 protein modulates, either directly or indirectly, different oncogenic pathways that support and promote survival, growth, and invasion of ovarian cancer cells. To evaluate the potential of this novel therapy, we have engineered a cancer-targeted nanoplatform and validated that DJ-1 siRNA delivered by this nanoplatform after intraperitoneal injection efficiently downregulates the DJ-1 protein in metastatic ovarian cancer tumors and ascites. In vivo experiments revealed that DJ-1 siRNA monotherapy outperformed cisplatin alone by inhibiting tumor growth and increasing survival of mice with metastatic ovarian cancer. Finally, three cycles of siRNA-mediated DJ-1 therapy in combination with a low dose of cisplatin completely eradicated ovarian cancer tumors from the mice, and there was no cancer recurrence detected for the duration of the study, which lasted 35 weeks.

Original languageEnglish (US)
Pages (from-to)1395-1405
Number of pages11
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number4
DOIs
StatePublished - Jun 2018

Keywords

  • DJ-1
  • cisplatin
  • combinatorial therapy
  • ovarian cancer
  • siRNA

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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