Synergistic chemotherapy for breast cancer and breast cancer brain metastases via paclitaxel-loaded oleanolic acid nanoparticles.

Breast cancer is the most common type of cancer in women. About 12% of all women in the United States will be diagnosed with breast cancer over their lifetimes. At the same time, incidences of brain metastases (BMs) are increasing and represents an emerging health threat. However, there is no effective chemotherapy for breast cancer brain metastases (BCBMs), which is largely due to lack of efficient delivery of anti-tumor drugs or drug combinations to the brain. In this study, oleanolic acid (OA), a natural pentacyclic triterpenoid compound with excellent anti-tumor activity, was found to form nanoparticles (NPs) and efficiently penetrate the brain for BCBMs treatment. Based on these findings, we developed a synergistic combinatorial chemotherapeutic regimen by formulating paclitaxel (PTX) into OA NPs and demonstrated that the resulting PTX- OA NPs effectively inhibited primary breast cancer and BCBMs in mouse xenografts. Collectively, this study introduces a new direction to treat primary breast cancer and BCBMs through non-invasive combination chemotherapy.