A novel navigated doxorubicin delivery formulation to breast cancer therapy

Abstract

Breast cancer (BC) is the most frequently diagnosed cancer and leading cause of the death in women. Current chemotherapy usually results in poor prognosis with low treatment efficacy and high side effects because of weak targeting specificity and fast elicitation of multidrug resistance (MDR). It is emergently needed to develop a novel BC targeting drug delivery formulation for the chemotherapy of BC and drug resistant BC. In our study, we screened out BC targeting 12-mer peptide (BSP1) from a phage-displayed peptide library, then a novel doxorubicin (DOX) delivery formulation (BSP1-Lipo-DOX-miR101) targeting BC automatically was synthesized and used in a series of experiments to test its efficacy of chemotherapy of BC and DOX resistant BC in vitro. The consequently results indicated that BSP1 bound to MCF-7 cells and BC tissues specifically and sensitively with high affinity, the BC automatically targeted drug vehicles exhibited its high specificity for BC targeting, marked suppression for the development of cell motility relevant microstructures, such as the polymerization of the pseudopodia and filopodia in MCF-7 and MCF-7/ADR cells. The novel drug formulation presented the satisfied therapeutic efficacy for BC therapy, particularly for DOX resistant BC in vitro. The results of western blot explored the potential mechanism by that BSP1-Lipo-DOX-miR101 inhibits the expression of EMT (epithelial/endothelial mesenchymal transition) and MDR relevant genes. Our current results provide a novel chemotherapeutic formulation with precise, satisfying therapeutic efficacy to improve the current poor BC clinical prognosis including drug resistant BC.

Keywords

• Breast cancer
• Targeted drug delivery
• Doxorubicin
• Multidrug resistance