Hyaluronic Acid-Decorated Graphene Oxide Nanohybrids as Nanocarriers for Targeted and pH-Responsive Anticancer Drug Delivery

A novel nanohybrid of hyaluronic acid (HA)-decorated graphene oxide (GO) was fabricated as a targeted and pH-responsive drug delivery system for controlling the release of anticancer drug doxorubicin (DOX) for tumor therapy. For the preparation, DOX was first loaded onto GO nanocarriers via pi-pi stacking and hydrogen-bonding interactions, and then it was decorated with HA to produce HA-GO-DOX nanohybrids via H-bonding interactions. In this strategy, HA served as both a targeting moiety and a hydrophilic group, making the as-prepared nanohybrids targeting, stable, and disperse. A high loading efficiency (42.9%) of DOX on the nanohybrids was also obtained. Cumulative DOX release from HA-GO-DOX was faster in pH 5.3 phosphate-buffered saline solution than that in pH 7.4, providing the basis for pH-response DOX release in the slightly acidic environment of tumor cells, while the much-slower DOX release from HA-GO-DOX than DOX showed the sustained drug-release capability of the nanohybrids. Fluorescent images of cellular uptake and cell viability analysis studies illustrated that these HA-GO-DOX nanohybrids significantly enhanced DOX accumulation in HA-targeted HepG2 cancer cells compared to HA-nontargeted RBMEC cells and subsequently induced selective cytotoxicity to HepG2 cells. In vivo antitumor efficiency of HA-GO-DOX nanohybrids showed obviously enhanced tumor inhibition rate for H22 hepatic cancer cell-bearing mice compared with free DOX and the GO DOX formulation. These studies suggest that the HA-GO-DOX nanohybrids have potential clinical applications for anticancer drug delivery.