Synergistic cytotoxic activity on breast cancer cells by tetrahydroxyquinone and photothermal therapy

In this work, the potential synergistic antineoplastic activity of tetrahydroxyquinone (THQ) in combination with photothermal therapy using gold nanoshells (AuNSHs) as photosensitizers and applying NIR light at 808 nm has been analyzed. To synthesize the AuNSHs, a core of PLGA and PVA was coated with oligochitosan, which was then mixed with a solution of gold seeds. The core-shell particles were obtained by a seeded-growth process in the presence of K-gold and ascorbic acid. These gold structures underwent an Ostwald ripening process and were subsequently PEGylated to increase their biocompatibility and colloidal stability. The diameter of these AuNSHs has an average of 131 ± 10 nm, a zeta potential of -20 ± 1 mV at physiological pH, a hydrodynamic diameter of 188 ± 2 nm, and a power absorption density of up to 93 W/cm³. Cell biology assays, using BT-474 breast cancer cell line, revealed a negligible decrease in metabolic activity when the cells were exposed to up to 1 mg/mL AuNSH, 100 μg/mL THQ or were irradiated for 15 min with an optical power (OP) of 2.0 W. The simultaneous administration of 1 mg/mL AuNSH and 100 μg/mL THQ reduced the cell viability only by ~17%. However, when following a photothermal therapy (AuNSH irradiated an OP of 2.0 W), 100 μg/mL THQ were added to the cells, their viability decreased significantly by ~61%, indicating a synergistic effect of the treatment. Using the Annexin V assay, it could be revealed that the majority of cells underwent apoptosis and only few died by necrosis.