Synergistic Delivery of Encapsulated Drugs to Hypoxia for Stemness Reduction in Triple-Negative Breast Cancer

Triple-negative breast cancer is a difficult-to-treat subtype of malignancy in which the progesterone receptor, estrogen receptor, and HER-2 protein are not expressed. Due to aggressiveness, increased tumor growth, metastasis, and hypoxic region formation are observed. These hypoxic, or low oxygen regions, express a higher population of cancer stem cells, furthering treatment difficulty. To combat this problem, we have utilized hypoxia-responsive polymersomes composed of a PEG-azo-PLA polymer. The polymersomes encapsulated doxorubicin (Dox), all-trans retinoic acid, or narciclasine. The polymersomes were characterized, and release in hypoxia was tested. Dox was combined with the two other drugs, and the synergy was determined. This synergistic combination was tested in 2D and 3D cell cultures to evaluate effectiveness. Compared to the unencapsulated drugs, the combinations showed greater effectiveness than individually in 2D and 3D cell cultures and reduced stemness.