Bio-Inspired Albumin Platform for Synergistic Co-Delivery of Tanespimycin, Dasatinib, and Quercetin and Enhanced Therapeutic Efficacy in Triple-Negative Breast Cancer.

Abstract

Despite increasing awareness of molecular subtypes of breast cancer, this heterogeneous malignant disease is still one of the leading causes of cancer death in women worldwide. Although receptor status may define the precise therapeutic targets, treatment of triple-negative breast cancer (TNBC) relies mainly on chemotherapy with accompanying side-effects. Thus, there is a need for the design and testing of more effective drug delivery systems and drug combinations. In this study, biomimetic self-assembled bovine serum albumin (BSA) capsules (Cs) co-loaded with a new drug combination, namely two drugs tanespimycin (T) and dasatinib (D), and natural compound quercetin (Q), were fabricated, and their anti-breast cancer effects were assessed. (T-D-Q)-BSA Cs were more active against TNBC cells compared to other types of breast cancer. Encapsulated drugs potentiated apoptotic cell death in TNBC cells compared to the effect of the free three-drug formulation. In TNBC cells with mutated TP53, (T-D-Q)-BSA Cs also induced necroptotic cell death accompanied by RAP1-mediated stimulation of NFκB activity and IL-6-related proinflammatory response. (T-D-Q)-BSA Cs also inhibited TNBC-based tumor growth in two zebrafish xenograft in vivo models. In conclusion, the efficacy of (T-D-Q)-BSA Cs as a novel therapeutic strategy to eradicate TNBC in vitro and in vivo was demonstrated.