Azobenzene-Incorporated Polymersomes for Control of Targeted Drug Delivery to Triple Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a resilient form of malignancy and lacks adequate targeted therapies. Hypoxia in the core of the solid tumors instigates invasive and metastatic cellular phenotypes, thereby exacerbating the problem. Immunofluorescence imaging indicated the overexpression of the receptor SLC7A11 on TNBC cells in hypoxia. We prepared a polymer conjugate of the anti-inflammatory agent sulfasalazine to target the TNBC cells employing hypoxia-responsive polymer nanoparticles (polymersomes). The polymersomes encapsulate the anticancer drug doxorubicin. This study investigated the stability and release characteristics of polymersomes incorporating hypoxia-responsive linkers with different electron densities. The polymersomes were characterized by encapsulation efficiency, size, integrity, and release rates in hypoxia. Their cytotoxicity was also assessed against MDA-MB-231 and patient-derived cells in monolayer and spheroid cultures.