Bifunctional liposome reduces chemotherapy resistance of doxorubicin induced by tumor hypoxia
Doxorubicin (DOX) Liposome is a widely used nano-medicine for colorectal cancer treatment. However, doxorubicin therapy increases the level of reactive oxygen species (ROS) in tumor cells, such as hydrogen peroxide (H2O2), which can stabilize hypoxia-inducible-factor-1α (HIF-1α). In a tumor hypoxic microenvironment, HIF-1 can up-regulate tumor-resistance related proteins, including P-glycoprotein (P-gp), Glucose transporter 1 (GLUT-1), matrix metalloproteinase 9 (MMP-9), leading to tumor tolerance of chemotherapy. The functional inhibition of HIF-1 can overcome this resistance and enhance the efficacy of tumor therapy. Here, we encapsulated one of most effective HIF-1 inhibitors, acriflavine (ACF), and DOX in liposomes (DOX-ACF@Lipo) to construct bifunctional liposomes. ACF and DOX, released from DOX-ACF@Lipo, could effectively suppress the function of HIF-1 and process of DNA replication, respectively. Consequently, the bifunctional liposome has great potential to be applied in clinic to overcome chemotherapy resistance induced by hypoxia.