Reductive response and RGD targeting nano-graphene oxide drug delivery system

Abstract

Cancer cell therapy using redox response and targeted drug delivery systems can increase therapeutic effects of anti-cancer therapy. Here, we report a redox-responsive drug carrier based on nanoscale Graphene Oxide (GO) loaded with Doxorubicin (DOX). In this drug carrier demonstration, we utilized Arginine-glycine-aspartic acid (RGD) peptide, aminated polyethylene glycol (6ARM-PEG-NH2, PEG-NH2) to functionalize the GO. To integrate the carrier with a redox responsive property, we utilized disulfide linkages (3,3′-dithiodipropionic acid (DTPA)), which can be cleaved by glutathione (GSH) combined with the PEG-NH2. Our results show that DOX is rapidly released in a pH = 5.50 PBS solution with GSH concentration of 10 mM. The drug-loading system (RGD-GO-PEG-S-S-DOX) combined with photo-thermotherapy possesses good inhibition activity of Hep-G2 cells at a relatively low concentration. When the concentration of RGD-GO-PEG-S-S-DOX was 1.56 μg/mL, the inhibition activity of Hep-G2 cells was 78%. Because tumor cells generally exhibit a higher concentration of GSH than normal ones, and tumor blood vessels are distorted and dilated, and the blood flow resistance tends to be large, tumor cells are more sensitive to temperature changes than normal tissues. Thus, drug delivery systems, like the one we studied, have potential applications in a therapeutic strategy for the treatment of liver cancer.