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-708^low 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-708^low tumor cells to impair metastasis. Together, our preclinical findings pr

SUBMITTER: Ramchandani D 

PROVIDER: S-EPMC6532393 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature