Synergistic effects of concurrent photodynamic therapy with indocyanine green and chemotherapy in hepatocellular carcinoma cell lines and mouse models

Photodynamic therapy (PDT) using an 808 nm laser irradiation with indocyanine green (ICG) has shown tumoricidal effects in a hepatocellular (HCC) orthotopic xenograft model. Recently, combining PDT with concurrent chemotherapy has shown synergistic outcomes and a better therapeutic effect for cancer treatment. In the present study, we utilized a combination of chemotherapy drugs and PDT using ICG in vitro and in vivo in a patient-derived orthotopic xenograft (PDoX) model.We independently performed PDT and chemotherapy with sorafenib or doxorubicin in the Huh-7 and Hep3b cell lines by increasing the sorafenib or doxorubicin concentration and increasing the total energy of 808 nm light. Subsequently, we combined the two treatments to confirm the effects on cell viability. The combination index (CI) was evaluated in vitro, and thereafter, in the HCC PDoX mouse model, 808 nm laser irradiation with intravenously injected ICG and chemotherapy using doxorubicin were performed for twelve days.The viability of the Huh-7 and Hep3B cell lines decreased rapidly as the concentration of sorafenib or doxorubicin increased and as the total energy of 808 nm light increased. The cell viability of the Huh-7 and Hep3b cell lines with combined PDT and chemotherapy was less than that with PDT or chemotherapy alone. The CI was <1 in the sorafenib- or doxorubicin-treated Huh-7 and Hep3b cell lines. In the HCC PDoX mouse model, tumor size was markedly decreased, and complete remission achieved compared to that of the single chemotherapy or PDT and control groups.The synergistic effect of concurrent PDT and chemotherapy in the HCC cell line and PDoX model was confirmed with no definite adverse effect. Concurrent PDT and chemotherapy could be applied in further preclinical studies.