Format

Send to

Choose Destination
Mol Cancer Ther. 2019 Mar;18(3):579-591. doi: 10.1158/1535-7163.MCT-18-0702. Epub 2019 Jan 24.

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

Author information

1
Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York.
2
Department of Radiology, Molecular Imaging Innovations Institute, Weill Cornell Medicine, New York, New York.
3
Department of Radiology, Molecular Imaging Innovations Institute, Weill Cornell Medicine, New York, New York. vim2010@med.cornell.edu cht2018@med.cornell.edu.
4
Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York.
5
Department of Cardiothoracic Surgery, Weill Cornell Medicine, New York, New York. vim2010@med.cornell.edu cht2018@med.cornell.edu.
6
Department of Cell and Developmental Biology, Weill Cornell Medicine, New York, New York.
#
Contributed equally

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.

PMID:
30679387
PMCID:
PMC6532393
[Available on 2019-09-01]
DOI:
10.1158/1535-7163.MCT-18-0702

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center