A Non-Invasive Combined Photothermal-Sonodynamic Therapy Using a Dual-Activated TiO2-Au Nanohybrid: A Competitive Alternative to the Invasive Radiotherapy.

BACKGROUND

Conventional radiotherapy (RT) is widely used to treat breast cancer (BC), although its use has been limited by ionizing damage and low repeatability. This study proposes a dual-activated, non-ionizing treatment strategy using TiO2-Au nanohybrids (NHs), triggered by near-infrared (NIR) light and ultrasound (US), to induce synergistic sonodynamic-photothermal therapy (SDPTT) as a minimally invasive alternative with therapeutic efficacy comparable to conventional radiotherapy (RT).

METHODS

TiO2-Au NHs were synthesized and thoroughly characterized using FESEM, TEM, UV-vis spectroscopy, zeta potential, and EDS analysis. Afterward, TiO2-Au NHs (50 μg mL-1) were used to treat MCF-7 BC cells with NIR, US, or both. MTT assays were performed to determine cell viability. DCFH-DA staining was applied to visualize ROS production. In following, MCF-7 BC cells as RT groups were treated with X-ray (4 Gy) with or without TiO2-Au NHs and MTT and ROS assays were conducted. Combination indices (CI) analysis was used to quantify synergy.

RESULTS

NIR or US alone had modest cytotoxicity, with viability of 74.3% and 78.2%, respectively. In the presence of TiO2-Au NHs, dual activation (SDPTT) significantly reduced viability to 38.4% (p < 0.01), accompanied by the highest ROS levels. This effect was comparable to RT + NH (37.9%) and superior to RT alone (72.1%). CI analysis revealed synergy in SDPTT (CI = 1.26) and RT + TiO2-Au NHs (CI = 1.44).

CONCLUSION

While radiotherapy stands as a well-established treatment method effective through ionizing radiation, TiO2-Au-mediated SDPTT introduces a supplemental non-ionizing strategy that combines heat generation with oxidative stress. The dual-activated nanostructure holds potential for safe and repeatable BC treatment, yet requires additional preclinical examination.