Characterization of synergistic anti-tumor effects of doxorubicin and p53 via graphene oxide-polyethyleneimine nanocarriers

Abstract

Co-delivery of chemical drugs and therapeutic genes for synergistic therapy provides a promising strategy to treat devastating diseases. However, the real-time coordination patterns between chemical drugs and therapeutic genes remain poorly understood. Herein, the complexes of doxorubicin/graphene oxide-polyethyleneimine/p53 plasmid (Dox/GO-PEI/p53) were fabricated and employed to investigate the synergistic manner between Dox and p53 in the inhibition of HeLa cell growth. GO was conjugated with PEI to form the GO-PEI backbone as the delivery vector. The GO backbone provided surfaces with a high specific area to load Dox via the π-π stacking interaction, and was able to release Dox significantly faster at pH 5.0 than at pH 7.0, while the positively charged PEI section of GO-PEI could condense plasmids into GO-PEI/DNA nanoparticles via the electrostatic interaction. The nanoparticles efficiently mediated the transfection of DNA in HeLa cells, with lower cytotoxicity compared to PEI/DNA nanoparticles. Furthermore, the complexes of Dox/GO-PEI/p53 released Dox and expressed p53 gene in a sequential manner, and showed successive inhibition of the in vitro growth of HeLa cells. This type of drug/GO-PEI/DNA complex can be employed as a platform to investigate the coordination pattern between chemical drugs and therapeutic genes for tumor therapy.