Redox and pH-responsive gold nanoparticles as a new platform for simultaneous triple anti-cancer drugs targeting

Abstract

Cancer is considered to be one of the leading causes of morbidity and mortality worldwide and nanotechnology was shown to have a unique potential to enhance the therapeutic performance of anticancer agents. A novel dual stimuli-responsive polyethylene glycol (PEG) block copolymer was synthesized for the decoration and stabilization of gold nanoparticles (NPs) to carry multiple anti-cancer drugs, doxorubicin (DOX), methotrexate (MTX) and 6-mercaptopurine (MP). DOX, MTX and MP were successfully loaded (the loading capacity of 37%, 12%, and 49%, respectively) into the NPs by ionic interaction (DOX and MTX) and disulphide-covalent bond formation (MP) in the polymeric shell of NPs. Furthermore, the triggered drugs release ability of NPs was shown through the comparison of simulated physiological and tumor tissue environments. The enhanced efficiency of the developed NPs and their targeted performance via MTX (target ligand of folate receptors) decoration were illustrated through the various cell cytotoxicity studies such as MIT assay, DAPI staining, and flow cytometry on various cancer cell lines with different levels of folate receptors. Our proposed idea in simultaneous delivery of three cytotoxic drugs with our newly designed PEGylated gold NPs may provide promising and novel prospect in cancer therapy. (C) 2017 Elsevier B.V. All rights reserved.