Liposomal delivery of DK14 chalcone analogue: A promising therapeutic strategy against triple-negative breast cancer

Abstract

Triple negative breast cancer (TNBC) is considered the most aggressive type of breast malignancy. TNBC management approaches remain limited, with a high risk of relapse and metastasis. Chalcone compounds are established for their anticancer activity. A recently patented novel chalcone compound (DK14) by our group has demonstrated a considerable activity against TNBC; however, its limited water-solubility is a challenge. In this study, we incorporated DK14 into a nano-liposomal formulation to enhance its solubility, safety and anticancer activity. The formulation was characterized in terms of particle size, zeta potential, drug entrapment, and release profile. Additionally, cytotoxicity, cell migration, colony formation and protein expression analysis were conducted. Furthermore, Angiogenesis study was performed using the chorioallantoic membrane (CAM) of the chicken embryo. DK14-liposomes demonstrated the ability to inhibit growth of TNBC cells and trigger apoptosis, accompanied by induction of BAX/BCL-2/Caspase-3 pathway. DK14-liposomes also exhibited an enhanced safety profile on non-tumorigenic mammary epithelial cells (MCF-10A) compared to free DK14 while suppressing cell migration and colony formation. Moreover, DK14-liposomes dysregulated PI3K/AKT/mTOR pathway, which is defective in TNBC; and significantly inhibited angiogenesis in ovo using a chiken embryo model. In conclusion, our results imply that DK14-liposomes have a substantial anticancer activity against TNBC with distinct anti-angiogenic properties.