Gold-doxorubicin nanoconjugates for overcoming multidrug resistance

This chapter considers drug-nanoparticle nanoconjugates by grafting doxorubicin (DOX) to the surface of poly (ethylene glycol) (PEG)-modified gold nanoparticles (AuNPs) through disulfide linkage for controlled drug delivery. We further evaluated the cytotoxicity and cellular uptake of Au-PEG-SS-DOX in multidrug resistance (MDR) cancer cells. The AuNPs size and surface morphology were characterized using transmission electron microscopy (TEM). TEM images illustrated the morphology of the functionalized AuNPs and indicated that they were well dispersed after conjugation with PEG and DOX. To verify the disulfide linkage in Au-PEG-SS-DOX, dithiothreitol (DTT) was added to a solution of Au-PEG-SS-DOX. The intracellular distribution of nanoparticles-loaded DOX and free DOX was investigated in drug-resistant HepG2-R cells using confocal microscopy. The cellular accumulation of Au-PEG-SS-DOX in MDR HepG2-R cells and the sensitive subline HepG2 was assessed with their intracellular content of AuNPs. The enhanced intracellular accumulation of Au-PEG-SS-DOX nanoconjugates may alternatively dysregulate mitochondrial DNA synthesis in the cytoplasm, thus inducing cell death. Copyright © 2017 Pan Stanford Publishing Pte. Ltd.