Nanoparticle delivery of miR-708 mimetic impairs breast cancer metastasis

Divya Ramchandani, Seung Koo Lee, Shira Yomtoubian, Myung Shin Han, Ching Hsuan Tung, Vivek Mittal

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Triple-negative breast cancer (TNBC) patients exhibit the worst clinical outcome due to its aggressive clinical course, higher rate of recurrence, and a conspicuous lack of FDA-approved targeted therapies. Here, we show that multilayered nanoparticles (NPs) carrying the metastasis suppressor microRNA miR-708 (miR708-NP) localize to orthotopic primary TNBC, and efficiently deliver the miR-708 cargo to reduce lung metastasis. Using a SOX2/OCT4 promoter reporter, we identified a population of miR-708low cancer cells with tumor-initiating properties, enhanced metastatic potential, and marked sensitivity to miR-708 treatment. In vivo, miR708-NP directly targeted the SOX2/OCT4-mCherryþ miR-708low tumor cells to impair metastasis. Together, our preclinical findings provide a mechanism-based antimetastatic therapeutic approach for TNBC, with a marked potential to generate miR-708 replacement therapy for high-risk TNBC patients in the clinic. To our knowledge, this gold nanoparticle-based delivery of microRNA mimetic is the first oligonucleotide-based targeted therapy for TNBC.

Original languageEnglish (US)
Pages (from-to)579-591
Number of pages13
JournalMolecular Cancer Therapeutics
Volume18
Issue number3
DOIs
StatePublished - Mar 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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