Nanoparticle Delivery of miR-708 Mimetic Impairs Breast Cancer Metastasis.

TitleNanoparticle Delivery of miR-708 Mimetic Impairs Breast Cancer Metastasis.
Publication TypeJournal Article
Year of Publication2019
AuthorsRamchandani D, Lee SKoo, Yomtoubian S, Han MShin, Tung C-H, Mittal V
JournalMol Cancer Ther
Volume18
Issue3
Pagination579-591
Date Published2019 03
ISSN1538-8514
KeywordsAnimals, 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.

DOI10.1158/1535-7163.MCT-18-0702
Alternate JournalMol Cancer Ther
PubMed ID30679387
PubMed Central IDPMC6532393
Grant ListT32 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)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065