In-vitro efficacy of indocyanine green-mediated photodynamic therapy in combination with cisplatin or etoposide

Abstract: Localizing the cytotoxic effects of cancer therapies to only affect the tumor cells is a goal in oncology, to maximize efficacy and minimize treatment-related morbidities. Most effective chemotherapeutic drugs have significant side effects due to off-target toxicity. By comparison, photodynamic therapy (PDT) is a localized therapy without significant systemic toxicity but may have limited efficacy. Hence, combining PDT with chemotherapy was investigated to determine if the anti-tumor effect of the latter could be enhanced. PDT using indocyanine green (ICG), activated by near-infrared light, was investigated in lung tumor cells in vitro in combination with cisplatin or etoposide (VP-16). The combination of cisplatin and ICG-PDT had significant concentration-dependent dark toxicity, with little additional cell kill after light exposure. Conversely, combination therapy comprising 5 μm VP-16, 50 μm ICG and 50 J/cm2 808-nm radiant exposure resulted in ~10% clonogenic cell survival compared to ~80% cell survival with either treatment alone. This potentially synergistic gain was achieved only when both treatments were given at the same time or when VP-16 was administered 4 h prior to PDT. VP-16 given 4 h post PDT did not show any added benefit over PDT alone.