# anti-miR-10b Nanodrug for Treatment of Breast Cancer Metastasis: Study in Companion Animals

> **NIH NIH R01** · MICHIGAN STATE UNIVERSITY · 2021 · $568,220

## Abstract

ABSTRACT
Nanoparticle-based technologies including theranostic nanomedicine are fast developing areas of biomedical
research offering unprecedented potential for cancer treatment. This application is designed to bring this
potential to translational level and investigate the application of our novel image-capable nanodrug for treatment
of metastatic breast cancer in a large animal model. Breast cancer metastasis is the main cause of mortality
among breast cancer patients, and for that reason the specific aims of this application respond to an unmet
clinical need. This proposed strategy is based on our discovery that the survival of metastatic cells crucially
depends on the high expression of microRNA-10b (miR-10b) and that miR-10b is responsible for metastatic cell
viability. With this discovery it became possible to kill these cells at metastatic sites by inhibiting miR-10b. This
is achieved using a nanodrug composed of anti-miR-10b antagomirs conjugated to dextran-coated magnetic
nanoparticles (termed MN-anti-miR10b). These nanoparticles serve as delivery vehicles for the antagomirs. Also,
the magnetic properties of these nanoparticles allow for monitoring of their delivery in vivo using magnetic
resonance imaging (MRI), which is an added value for clinical implementation of this therapeutic approach. In
pre-clinical studies in mice, we showed delivery of MN-anti-miR-10b to established metastases in the lymph
nodes, lungs, bone and brain. Pilot studies in companion cats showed the delivery of the nanodrug to the
metastatic lesions after intravenous injection. Therapeutic studies in the murine model of human MDA-MB-231
TNBC showed that delivery of MN-anti-miR10b to lymph nodes with established metastases resulted in arrest of
metastatic growth by halting tumor cell proliferation and triggering apoptosis. When combined with a low-dose
chemotherapy, MN-anti-miR10b caused complete elimination of lymph node metastases with no evidence of
systemic toxicity after just four weekly treatments. Next, we showed the utility of the nanodrug in combination
with low-dose chemotherapy for treatment of established lung metastases corresponding to Stage IV of human
disease in immunocompetent murine model (4T1). We found that six weekly treatments were sufficient to cause
complete regression of pre-existing lung metastases with no further dissemination to other organs in the
remaining animals.
With an outlook to clinical translation of our studies, in this application we propose to test our nanodrug strategy
in large animals with spontaneous metastatic breast cancer (companion cats). Studies proposed here will serve
as a necessary step towards first-in-human trials, because they will prove successful delivery of the nanodrug in
large animals, which are anatomically and physiologically distinct from the murine models tested to date.
Furthermore, these studies will provide us with additional information on PK/PD parameters in a large animal
model. Finally, therapeu...

## Key facts

- **NIH application ID:** 10265643
- **Project number:** 1R01CA261691-01
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** ANNA MOORE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $568,220
- **Award type:** 1
- **Project period:** 2021-07-13 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10265643

## Citation

> US National Institutes of Health, RePORTER application 10265643, anti-miR-10b Nanodrug for Treatment of Breast Cancer Metastasis: Study in Companion Animals (1R01CA261691-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10265643. Licensed CC0.

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