Combination treatment of hepatitis C virus-associated hepatocellular carcinoma by simultaneously blocking genes in multiple organelles via functionally engineered graphene oxide

Abstract

Chemical reagents are widely used to block disease development, including tumor progression and increase in abnormal cell populations; however, their consistent usage is limited owing to drug-related side effects and resistance. Although strategies to enhance the intracellular delivery of anticancer drugs, even at low concen-trations, and decrease their undesired side effects have been developed, practical approaches for liver cancer are still limited. Combination therapy has become a solution for improving chemotherapeutic efficacy. Here, we designed a dual-therapeutic platform by engineering graphene oxide (GO) as a multi-functional co-delivery carrier that targets multiple organelles in cells. It delivers two therapeutic reagents as a single vehicle while simultaneously blocking genes in the nucleus and cytoplasm. We adopted a xenograft mouse model of hepatitis C virus infection to verify the therapeutic efficacy of this combinatorial approach. Our strategy successfully sup-pressed tumor growth by enhancing the intracellular accumulation of anticancer drugs even at one-tenth of the conventional dosage of drugs. Simultaneously, the dual-treat method showed a twofold therapeutic efficiency compared with single-drug treatment. By facilitating a combination of individual pharmacological effects, the present functional GO-based delivery system could be a promising multimodal therapeutic platform owing to its high stability, biocompatibility, and multifunctionality.