Nanoparticle Delivery of miR-708 Mimetic Impairs Breast Cancer Metastasis
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-mCherry+ 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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Mar 01, 2019
- Source ID
- 10.1158/1535-7163.mct-18-0702
Entities
People
- Ching-Hsuan Tung
- Divya Ramchandani
- Myung Shin Han
- Seung Koo Lee
- Shira Yomtoubian
- Vivek Mittal
Organizations
- United States Department of Defense
- Weill Cornell Medicine