Presently, chemotherapy is the mainstay therapy for metastatic cancer. However, considering the disadvantages of standard chemotherapy, e.g. non-specific delivery, toxicity to healthy tissues, and the potential for chemoresistance, we envision a future in which chemotherapy is complemented or replaced by alternative approaches. In response to this vision, we designed a nanodrug consisting of magnetic nanoparticles conjugated to miR-inhibiting oligonucleotides (MN-anti-miR) for the specific inhibition of selected miRNAs in primary tumors and metastases. In our earlier studies, we demonstrated that intravenous injection of MN-anti-miR10b led to inhibition of the well-known metastamir miR-10b in the primary tumors and lymph node metastases in a murine model of metastatic breast cancer. We also showed that, whereas delivery to the primary tumor resulted in complete prevention of tumor cell dissemination to secondary organs, delivery to the lymph nodes arrested metastatic progression. We also performed longitudinal studies to further expand the therapeutic relevance of miR-10b by combining low-dose doxorubicin (Dox) and the MN-anti-miR10b nanodrug for the treatment of local and distant metastatic breast cancer. We showed that, by merging the pro-senescence trigger provided by low-dose doxorubicin and the anti-metastatic, pro-apoptotic, and anti-proliferative effects of the nanodrug, it is possible to achieve complete and persistent regression of metastatic disease.

Zdravka Medarova, PhD, is an Associate Professor of Radiology at Harvard Medical School.  Her research focuses on the development and testing of image-guided therapy of metastatic prostate cancer.  Her work on the design and application of ultrasmall iron oxide nanoparticles as imaging-capable carriers of siRNA to tumors has generated substantial interest in the research community.  More recently, her lab developed magnetic nanoparticles as delivery vehicles of miRNA-targeted therapy to breast tumors. This work resulted in a publication in Oncogene, and award from the Breast Cancer Alliance and an R01 award from the NCI.