Fabrication of graphene oxide-β-cyclodextrin nanoparticle releasing doxorubicin and topotecan for combination chemotherapy

Controlled delivery of dual chemical drugs may increase the efficiency of chemotherapy. In this work, doxorubicin (DOX) was bound to adamantanecarboxylic acid (AD-COOH) through covalent linkage to form AD-DOX, while graphene oxide (GO) was modified by ethylenediamino-β-cyclodextrin (EDA-CD) to form graphene oxide-β-cyclodextrin (GO-CD), then GO-CD was assembled with as-produced AD-DOX via host–guest interaction. In contrast to the conjugation of DOX via covalent linkage, topotecan (TPT) was loaded onto GO through π–π stacking interaction. It was found that TPT/GO-CD/AD-DOX nanoparticles synchronised the delivery of DOX and TPT, and pH value played a critical role in determining the release profiles of dual drugs. Moreover, in vitro cellular investigations proved that TPT/GO-CD/AD-DOX nanoparticles were superior to free drugs and single-drug loaded nanoparticles in inhibiting the growth of HeLa cells. As a kind of injectable biomaterials, this controlled drug delivery device offers a solution to simultaneous delivery of dual chemical drugs in cancer lesion positions. Authors expect that this platform can be exploited for controlled delivery of various drug combinations for combination chemotherapy.