Title | Nanoparticle Delivery of miR-708 Mimetic Impairs Breast Cancer Metastasis. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Ramchandani D, Lee SKoo, Yomtoubian S, Han MShin, Tung C-H, Mittal V |
Journal | Mol Cancer Ther |
Volume | 18 |
Issue | 3 |
Pagination | 579-591 |
Date Published | 2019 03 |
ISSN | 1538-8514 |
Keywords | Animals, Biomimetics, Cell Proliferation, Female, Gene Expression Regulation, Neoplastic, Gold, Heterografts, Humans, Metal Nanoparticles, Mice, MicroRNAs, Neoplasm Metastasis, Neoplasm Recurrence, Local, SOXB1 Transcription Factors, Triple Negative Breast Neoplasms |
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 cancer cells with tumor-initiating properties, enhanced metastatic potential, and marked sensitivity to miR-708 treatment. , miR708-NP directly targeted the SOX2/OCT4-mCherry+ miR-708 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. |
DOI | 10.1158/1535-7163.MCT-18-0702 |
Alternate Journal | Mol Cancer Ther |
PubMed ID | 30679387 |
PubMed Central ID | PMC6532393 |
Grant List | T32 GM008539 / GM / NIGMS NIH HHS / United States U01 CA188388 / CA / NCI NIH HHS / United States UL1 TR000457 / TR / NCATS NIH HHS / United States UL1 TR002384 / TR / NCATS NIH HHS / United States |
Related Institute:
Molecular Imaging Innovations Institute (MI3)