Hyaluronic acid conjugated graphene oxide for targeted drug delivery

Nano-sized graphene oxide (GO) is functionalized with adipic acid dihydrazide to introduce amine groups, and then hyaluronic acid (HA) is covalently conjugated to GO by the formation of amide bonds. The resulting HA-grafted GO (GO-HA) has negligible hemolytic activity and very low cytotoxicity towards HeLa and L929 cells, and it can be effectively taken up by cancer cells through receptor-mediated endocytosis. The histological, hematological and biochemical analysis results suggest no perceptible toxicity of GO-HA in mice at a high exposure level of 10 mg kg(-1) and at an exposure time of up to 10 days. Doxorubicin (DOX) can be efficiently loaded on the GO-HA, and the resulting GO-HA/DOX exhibits notable cytotoxicity to HeLa cells. The in vivo drug delivery capability of GO-HA is demonstrated by following the tumor growth in mice after intravenous administration of GO-HA/DOX. The results indicate that GO-HA can efficaciously deliver DOX to the tumors and suppress tumor growth. (C) 2013 Elsevier Ltd. All rights reserved.