Near-infrared phototherapy for patient-derived orthotopic xenograft model of hepatocellular carcinoma in combination with indocyanine green

Background: Hepatocellular carcinoma notably takes up and retains indocyanine green (ICG). Here, we investigated whether patient-derived orthotopic xenograft of hepatocellular carcinoma could accumulate ICG and show full remission via phototherapy. Methods: NIR light and ICG were tested for cytotoxicity in cancerous cell lines (Huh-7, Hep3B). Patient-derived orthotopic xenograft (PDoX) mice were subjected to phototherapy comprising of daily NIR exposure (0.5-1.75 W/cm(2)) and intravenous injection of ICG (5-20 mg/kg(2)). Moreover, NIR laser was flashed on individual mouse until hepatocellular carcinoma completely loss the fluorescence, as determined by NIR camera. Results: Cytotoxicity increased in response to the input energy, but insufficient energy (< 150 joule/cm(2)) was irresponsive at all irradiances. NIR irradiance in the range of 0.5-1.75 W/cm(2) took 5-7 days to elicit complete remission from PDoX mice in combination with 20 mg/kg ICG. In contrast, phototherapy could completely ablate hepatocellular carcinoma at 5-15 mg/kg ICG. Conclusions: ICG could potentiate the tumoricidal ability of NIR light in a dose-dependent manner, and vice versa. Regardless of ICG dosage, however, phototherapy treated group showed a relatively high survival rate compared to the non-treated group. Notably, real-time phototherapy could halve the effective ICG dosage for full remission of deep-seated tumor.