Apoptosis induction and inhibition of drug resistant tumor growth in vivo involving daunorubicin-loaded graphene–gold composites

Abstract

Daunorubicin (DNR) loaded graphene-gold nanocomposites offer a novel strategy for inducing apoptosis in drug resistant leukemia cells (K562/A02; KA). In vitro and in vivo investigations on xenografted tumors in KA nude mice demonstrate that the combination of monoclonal P-glycoprotein (P-gp) antibodies and DNR anticancer drug loaded on graphene-gold nanocomposites (GGN) is an efficient drug delivery vector, with remarkable targeting and binding properties towards drug resistant KA cell lines, and induces apoptosis of KA cells and inhibits tumor growth in KA nude mice. Cellular treatment with DNR-loaded GGN remarkably reduced drug resistant-related P-gp expression and activated apoptosis-related caspase protein expression in KA cells. Cell apoptosis provoked in vitro by such nanocomposites corresponds to a rapid induction of active caspase 8,3 activities and stimulation of poly-(ADP-ribose) polymerase (PARP) proteolytic cleavage. In vivo studies indicate that DNR-loaded GGN nanocomposites effectively overcome the inhibition of drug resistant leukemia cell-induced tumor growth in KA nude mice. This nanocomposite raises the possibility of modulating apoptosis in cancer cells, and of inhibiting tumor growth, showing that nanocomposites of this kind have promising applications in efficient multifunctional therapy.