Mitochondria-targeted docetaxel loaded DQAsomes for the treatment of multi-drug resistant breast tumor: In vitro and in vivo studies

Abstract

Multidrug resistance (MDR) has become a major obstacle in the successful chemotherapy of breast cancer which is the leading cause of death in women. In our recent work, we successfully demonstrated the remarkable anticancer potential of docetaxel-loaded DQAsomes (DOC-DQAsomes) against MDR-resistant MDA-MB-231 and normal MCF-7 breast cancer cell lines. However, the in vitro performance of any drug delivery system does not guarantee similar behaviour in vivo. Thus the present work was planned to assess the in vivo performance of prepared DOC-DQAsomes and to generate additional evidence for their anticancer activity. In vitro, cell uptake studies, ROS assay and mitochondrial targeting assays were carried out on DQAsomes along with in vivo antitumor efficacy in the MDR-resistant MDA-MB-231 tumor-induced SCID mice. Rhodamine-labelled DQAsomes were readily taken up by MDA-MB-231 cells in a time-dependent manner. Further DOC-DQAsomes showed an increment in ROS generation and reduction in mitochondrial membrane potential which revealed their anticancer activity. Additionally, DOC-DQAsomes demonstrated remarkable in vivo antitumor activity in tumour-bearing mice. The anticancer potential of DOC-DQAsomes was attributed to their ability to reduce mitochondrial membrane potential, generation of ROS and in turn release cytochrome C from mitochondria, leading to enhancement in apoptosis of MDA-MB-231 cells. Moreover, the treatment of DOC-DQAsomes did not affect the survival rate of xenografts which is the major drawback of many anticancer formulations. Thus DOC-DQAsomes could be the choice of treatment in MDR-resistant breast cancer demonstrating activity through the mitochondria signaling pathway.