Co-delivery of Liposomal Ketoconazole and Bevacizumab for Synergistical Inhibition of Angiogenesis Against Endometrial Cancer.

In this study, we designed a novel formulation based on liposomes for the co-delivery of cancer-derived exosome inhibitor (ketoconazole, Keto) and angiogenesis inhibitor (bevacizumab, mAb). The designed Combo-Lipo formulation was systematically characterized, exhibiting a uniform average particle size of 100 nm, as well as excellent serum and long-term physical stabilities. The cell viability assay revealed that Combo-Lipo treatment significantly reduced the viability of cancer cells compared to free drugs. Moreover, liposomes effectively inhibited angiogenic mediators and reduced tumor immune suppressive factors. The Combo-Lipo formulation demonstrated potent downregulation of angiogenic factors and synergistic effects in suppressing their production. Furthermore, liposomes inhibited tumor-associated macrophages (TAMs), leading to decreased expression of tumor-promoting factors. Together, these findings highlighted the promising characteristics of Combo-Lipo as a therapeutic formulation, including optimal particle size, serum stability, and potent anti-cancer effects, as well as inhibition of angiogenic mediators and TAMs toward treating endometrial cancer.