Cyclic RGD-modified chitosan/graphene oxide polymers for drug delivery and cellular imaging

Polymers based on cyclic RGD-modified chitosan/graphene oxide are investigated in this paper as an innovative type of drug delivery system for hepatocellular carcinoma-targeted therapy and imaging. The system was prepared using a simple noncovalent method by coating drug-loaded graphene oxide (GO) with cyclic RGD-modified chitosan (RC). The results show that an efficient loading of doxorubicin (DOX) on GO (1.00 mg/mg) was obtained. The system exhibits a pH-responsive behavior because of the hydrogen bonding interaction between GO and RC, and may be very stable under physiological conditions but with release at a lower pH (tumor environment). In addition, cellular uptake and proliferation studies using hepatoma cells (Bel-7402, SMMC-7721, HepG2) indicated that the cRGD-modified chitosan/graphene oxide polymer could recognize hepatoma cells and promote drug uptake by the cells, especially for cells overexpressing integrins. Together, these results demonstrate that the RC/GO polymers provide a multifunctional drug delivery system with the ability to target hepatocarcinoma cells, and are pH-responsive and can be efficiently loaded with a number of therapeutic agents for biomedical applications. (C) 2014 Elsevier B.V. All rights reserved.