Interaction of dye-enhanced photothermotherapy and chemotherapy in the treatment of cancer: an in vitro study

Doxorubicin (DOX), widely used in cancer chemotherapy, is limited by drug resistance and cardiac toxicity. Hyperthermia can aid the functionality of DOX, but current external heat delivery methods are hard to apply selectively and locally. Indocyanine green (ICG) absorbs near infrared light at 808nm (ideal for tissue penetration) and emits the energy as heat. These properties make it an ideal agent for rapid and localized hyperthermia. The purpose of this study was to investigate the in vitro cytotoxic effect of combined chemotherapy and hyperthermia to a DOX resistant ovarian cancer cell line (SKOV-3). The effects of laser-ICG photothermotherapy, which induces localized rapid heating, and an incubator, which induces a slow rate of heating, were compared. Cells were subjected to different concentrations of DOX and either 60 minutes in a 43°C incubator or to one minute at 43°C using 5μM of ICG and 808nm laser. SRB assay was used to measure cell growth. ICG itself without laser irradiation was not toxic to the cells. DOX by itself was cytotoxic with an IC50 about 5μM. Both incubator and laser-ICG Hyperthermia in combination with DOX achieved significantly greater growth inhibition at all DOX concentrations compared to DOX alone. DOX combined with 60 minutes 43°C incubation lowered DOX IC50 to about 1μM. The DOX IC50 value with one minute laser-ICG was even lower (0.1μM) suggesting a synergistic effect between DOX and laser-ICG photothermotherapy. In conclusion, the combination of localized heating and chemotherapy may provide a valuable tool for cancer treatment with minimized toxic effect.

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