Synergistic approach to combat triple-negative breast cancer: Ti3C2/ TiO2-based photothermal therapy combined with sonodynamic effect for tumor ablation

The incidence rate of female breast cancer in China ranks first in the world, where the five-year survival rate after chemotherapy for triple -negative breast cancer (TNBC) is less than 12%, and there is an urgent need to explore more novel combination therapies to augment efficacy of traditional chemotherapeutic modalities. In this study, a nanodrug was prepared by loading doxorubicin (DOX) and encrusting with calcium carbonate (CaCO3) on twodimensional Ti3C2/TiO2 nanosheets (TDC). This study aims to investigate their anti -tumor effect of TDC in combination with photothermal and sonodynamic therapy. Uptake of TDC nanoparticles into TNBC cells and a pH -dependent release pattern of Ca2+ were observed. Critically, cell viability was remarkably inhibited by TDCmediated combinatory photothermal and sonodynamic therapies. A subcutaneous tumor model of triple -negative breast cancer in nude mice was established to evaluate the efficacy of TDC in vivo photoacoustic imaging and anti-TNBC. The results show that TDC elicited photoacoustic imaging of tumor and suppressed tumor growth in xenograft models. Immunohistochemistry and immunofluorescence staining of tumor tissues revealed that TDCbased combinatory photothermal and sonodynamic therapies induced elevated expression of apoptosis relevant proteins. Furthermore, by establishing the mouse model of bilateral TNBC, we discovered that the immune response was activated in tumor microenvironment after combination therapy. Collectively, our study revealed that combinatory strategy of photothermal and sonodynamic therapies based on TDC suppressed proliferation and induced apoptotic cell death of breast cancer cells. Our findings provide new insights into exploiting novel therapies based on TDC in order to provide a possible safe and effective method for the treatment of TNBC.