Hyaluronic acid-modified liposomes Co-encapsulating curcumin and mifepristone to enhance anti-breast cancer efficacy

The tumor microenvironment (TME), which is composed of stomal cells, tumor cells, numerous cytokines and growth factors and directly related to poor prognosis, has been proven to play an important role in the development of breast cancer. Considering that CD44 receptors are over-expressed on the surface of breast cancer cells and cancer-associated fibroblasts (CAFs), the hyaluronic acid (HA)-modified liposomes could simultaneously target them via HA-CD44-mediated endocytosis. In this study, mifepristone (RU486) and curcumin (CUR) were successfully encapsulated into the HA-modified liposomes using the thin film evaporation method. The physical characteristics, such as particle size, zeta potential, encapsulation efficiency, drug loading capacity, were systematically analyzed. To mimic real TME for in vitro and in vivo evaluation, we established MCF-7+NIH/3T3 dual-cell model and 4T1+ NIH/3T3 co-injecting mice model. The results indicated that CUR&RU486/HA-LIPs were spherical with uniform particle size, and proved to be readily uptake by both of MCF-7 cells and CAFs. Compared with other groups, CUR&RU486/HA-LIPs exhibited stronger anti-proliferation and anti-migration ability in vitro. Additionally, the in vivo results showed that mice treated with CUR&RU486/HA-LIPs demonstrated smaller tumor volume, less angiogenesis, lower extracellular matrix (ECM) deposition, weaker lung metastasis than other groups. Hence, the combination therapy based on HA-modified liposomes might be an effective therapeutic approach to against breast cancer.