Design and Development of Graphene Oxide Nanoparticle/Chitosan Hybrids Showing pH-Sensitive Surface Charge-Reversible Ability for Efficient Intracellular Doxorubicin Delivery

A novel graphene oxide nanoparticle (GON)-based drug delivery system containing GONs as carriers of anticancer drugs and chitosan/dimethylmaleic anhydride-modified chitosan (CS/CS-DMMA) as surface charge-reversible shells is fabricated via the classic self-assembly of the deprotonated carboxyl of GONs and the protonated amine of the CS backbone by electrostatic interaction, and CS-DMMA serves as the outmost layer. In this GON-based drug delivery system, the GON cores as desired carriers might adsorb doxorubicin hydrochloride (DOX) via the π–π stacking interaction between the large π conjugated structures of GO and the aromatic structure of DOX. Meanwhile, the chitosan-based polyelectrolyte shells served as a smart protection screen to evade the premature release of the as-loaded DOX in normal extracellular condition, and then, the release of DOX was accelerated because of the detachment of chitosan coating at low pH. Furthermore, the re-exposure of amino groups after hydrolysis of CS-DMMA endowed the drug...