Inhibition of cancer cell proliferation by adenosine triphosphate-triggered codelivery system of p53 gene and doxorubicin

Abstract

The codelivery of drugs and genes by stimuli-responsive nanocarriers is a promising strategy for achieving an effective cancer treatment. In this study, an adenosine triphosphate (ATP)-responsive nanosystem was constructed to codeliver doxorubicin (DOX) and p53 gene based on an ATP-triggered aptamer and polyethyleneimine (PEI). In this system, DOX interacts with the GC-rich motif of duplex formed by the aptamer and its cDNA sequence. Then, a ternary nanocomplex DOX-Duplex/PEI/p53 was constructed using cationic carrier PEI25K for facilitating the intracellular delivery and release of p53 gene and DOX. The DOX-Duplex/PEI/p53 nanocomplex was found to possess an efficient anticancer effect, which was attributed to the ability of the system to trigger cell apoptosis and meanwhile block the cell cycle at G2 phase. The favorable antiproliferative effect was found to be associated with the rapid DOX and p53 gene release in response to the intracellular ATP concentration and the synergistic effect of therapeutic drug and gene.