A novel polymeric micelle-decorated Fe3O4/Au core–shell nanoparticle for pH and reduction-responsive intracellular co-delivery of doxorubicin and 6-mercaptopurine

Abstract

Cancer is one of the most common health problems which leads to death in the world, and an impressive approach to clinical cancer treatment is combination chemotherapy. To address this concern, multi-anticancer agents have been used simultaneously to achieve synergistic effects with decreasing toxic side effects of drugs owing to the administration of low drug dose. Moreover, nanosized drug delivery systems (DDS) have been proposed for targeting tumor tissue because of their enhanced permeability and retention (EPR) effect, improved drug bioavailability and long circulation time. For this purpose, we designed novel Au-coated Fe₃O₄ nanoparticles (NPs) capped with pH/redox dual-responsive nanomicelles (NMs) for intracellular co-delivery of 6-mercaptopurine (MP) and doxorubicin (DOX). The developed nanocarrier exhibited many favorable capabilities such as a narrow size distribution range (96 nm), high drug loading capacities (31% for DOX and 14% for MP), and stimuli-responsive drug release. The high loading capacity of MP was due to the covalent grafting of a disulfide agent to the polymeric segment as a redox-responsive platform for loading of MP. The anticancer performance of the nanocarrier was also assessed by various apoptosis tests and a cellular uptake study. According to the obtained results, we anticipate that the developed smart nanocarrier can be applied for co-delivery of multi-anticancer drugs to minimize the side effects of drugs.