Peptide conjugated hypoxia-responsive nanoparticles to decrease triple-negative breast cancer stemness.

TNBC (triple-negative breast cancer) tumors, diagnosed in 10-15% of patients, have limited treatment options due to the lack of hormone receptors. To address this, we developed targeted hypoxia-responsive polymersomes containing the stemness inhibitor Napabucasin (NAPA) and the anticancer drug Doxorubicin (DOX). The polymersomes showed a synergistic effect of NAPA and DOX in regulating cell proliferation, with higher effectiveness in hypoxia than Normoxia. Also, we observed a reduction in the cancer stemness marker in 2D monolayer and 3D spheroids with targeted combination drug therapy compared to the control. Furthermore, the targeted combination therapy reduced tumor size and cancer stemness markers in TNBC patient-derived xenograft (PDX) mice. The combination of NAPA and DOX has shown promising results in controlling the growth of MDA-MB-231 cells and TNBC PDX cells. Encapsulation of NAPA and DOX enhances the release of drugs in hypoxic conditions, thereby killing the cancer cells and reducing cancer stemness markers.