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

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).

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.

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).

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.