Cumulative Effect of a Gold-Poly(o-aminophenol) Nanocomposite and Doxorubicin in Photothermal Therapy, Sonodynamic Therapy, and Chemotherapy of Breast Cancer (MCF-7 Cell Line)

Introduction: Nowadays, the applications of non-invasive treating cancer methods such as photothermal therapy (PTT) and sonodynamic therapy (SDT) are increasing. These treatments use photo/sonosensitizers, which are activated after being exposed by laser light irradiation and ultrasound (US) exposure, respectively. Methods: Herein, a gold-poly (ortho-aminophenol) nanocomposite (Au-PoAP NC) with a spherical shape, a diameter of 46±8 nm was synthesized and evaluated as an 808-nm laser photosensitizer (with 30% photothermal efficiency) and a sonosensitizer upon US exposure. Additionally, Au-PoAP NC was appraised with doxorubicin (as a chemotherapy agent) for treating breast cancer cells. The MTT test was done for cell-toxicity evaluation of Au-PoAP NC, doxorubicin, and Au-PoAP NC with doxorubicin with or without irradiation and US exposure (separately and synchronously). Results: The results proved that light irradiation and US exposure (separately and synchronously) of Au-PoAP NC with doxorubicin significantly enhanced the cell toxicity in other treatment groups. Moreover, cytotoxicity of Au-PoAP NC, doxorubicin, and Au-PoAP NC with doxorubicin toward MCF-7 cells upon PTT and/or SDT was investigated from the aspect of reactive oxygen species (ROS) formation. Calculating the combination indices revealed that synchronous administration of Au-PoAP NC and doxorubicin and light irradiation and US exposure represented a synergistic therapeutic manner for treating cancer cells. Conclusion: This study proved that the synchronous combination of PTT and SDT using Au-PoAP NC with doxorubicin would be an exemplary approach for treating the breast cancer cell line of MCF-7.