Nano Liposomal Formulation for A Novel Chalcone Compound as A Potential Anticancer Delivery System for Triple-Negative Breast Cancer

Abstract

Triple negative breast cancer is the most aggressive type of breast malignancy accounting for 15-20% of all breast cancer cases. Treatment of TNBC remains limited, with a high risk of relapse and metastasis to other organs. On the other hand, compound DK14 has been identified and screened biologically and proven to be a potent anticancer agent against HER-2 positive and triple-negative breast cancers. However, like many other anticancer agents, compound DK14 has poor water solubility, hindering its further development. Hence, we developed a nano liposomal formulation encapsulating compound DK14 to enhance its solubility, safety, and anticancer activity. The liposomal formulation has been characterized by particle size, PDI, and zeta potential. Furthermore, DK14 EE% was found to have a high value of 89%. The pharmacological screening of DK14 liposomes has revealed that it has inhibited the proliferation of TNBC cell lines and induced clear morphological changes that indicate apoptosis. Moreover, DK14 liposomes have exhibited an enhanced safety profile on MCF-10A; in addition, it has demonstrated a higher selectivity towards TNBC cells over normal cells compared to the free drug. Furthermore, DK14 liposomes have inhibited the migration of TNBC cell lines and colony formation, indicating their ability to inhibit tumor growth and metastasis in vivo. The investigations of the molecular mechanisms by which DK14 liposomes have exerted their effects have revealed that DK14 liposomes have induced apoptosis via deregulation of the BAX/BCL-2/Caspase-3 pathway. Further, DK14 liposomes have downregulated the PI3K/AKT/mTOR pathway, which is defective in TNBC. The in ovo screening has revealed that DK14 liposomes have inhibited the angiogenesis of the CAM model. Our findings implied that DK14 liposomes have a substantial anticancer activity against TNBC and have provoked apoptosis via the PI3K/AKT/mTOR pathway. Keywords: DK14 liposomes, TNBC, PI3K/AKT/mTOR pathway, Apoptosis, In ovo.