Targeting miR-10b in Breast Cancer Bone Colonization Model Using Image-Guided Nucleic Acid-Based Therapeutics.

Background/

Objectives

Breast cancer is the most frequently diagnosed cancer among women worldwide and a leading cause of cancer-related death. Despite the use of bisphosphonates, RANKL inhibitors, chemotherapy, and available endocrine therapies, the five-year survival rate for patients with bone metastases remains approximately 20-30%, underscoring the urgent need for novel, metastasis-specific therapeutic strategies. Recent studies demonstrated that miR-10b can serve as an attractive therapeutic target for the treatment of metastatic breast cancer, particularly in the context of bone metastasis. This study aimed to test antimir-10b therapeutics in a mouse model of breast cancer bone metastasis.

Methods

We utilized a previously developed dextran-coated iron oxide nanoparticle-based platform for delivery of antisense anti-miR-10b oligonucleotides to bone metastases. The magnetic properties of the nanoparticles allowed for in vivo imaging of therapeutic delivery to metastatic tumors.

Results

We showed the delivery of the therapeutics in the bone colonization model by in vivo imaging as well as significant survival benefits in injected animals. There was a significant inhibition of miR-10b following treatment that resulted in significant upregulation of the downstream target HOXD10 in vitro and a similar trend in vivo. Repeated dosing of the therapeutics was well tolerated, and no systemic toxicity was observed, supporting the safety profile of this approach.

Conclusions

Collectively, these studies demonstrated that targeting miR-10b using an image-guided anti-miR-10b nanotherapeutic represents a promising and translatable strategy for targeting breast cancer bone metastases.