Graphene oxide–Fe3O4 nanocomposite for combination of dual-drug chemotherapy with photothermal therapy

Abstract

Multi-modal strategies may enhance anticancer efficacy by overcoming tumor drug resistance due to different anticancer pathways and mechanisms. Herein, a novel method of synthesizing ultra-fine graphene oxide (uGO)–magnetic nanoparticle (MNP) composites is presented. This composite is fabricated by combination of a simple and effective chemical deposition with further oxidation of iron ions on a carboxylated uGO base, followed by coating oleic acid on MNPs. Two anticancer drugs, camptothecin (CPT) and methotrexate (MTX), are separately bound to uGO sheets and the carboxyl terminals of uGO on the hybrid, forming a superparamagnetic & dual drug-loaded MTX@uGO–COOH@MNP@OA@CPT nanocomposite. The size of the composite is approximately 80 nm by DLS. The entrapment efficiencies of MNPs, CPT, and MTX reach approximately 458 mg g⁻¹, 682 mg g⁻¹, and 896 mg g⁻¹, respectively. In vitro release and apoptotic assay results show that the nanocomposite can cause the apoptosis and death of HepG2 cells by preferentially releasing drugs to the tumor microenvironment. The tumor inhibitory rate of 73.9% in S-180 sarcoma-bearing Balb/c mice suggests that the combination of nanocomposite-mediated dual drug synergic chemotherapy with photothermal therapy has remarkable therapeutic potential against drug-resistant tumors.