Thermoelectric Nanoheterojunction-Mediated Multiple Energy Conversion for Enhanced Cancer Therapy

Electron-hole recombination and exogenous local hypoxia both impede the effectiveness of thermoelectric tumor catalytic therapy. Here, a thermoelectric heterojunction (Pt-TiO_2-<i>x</i>/Ti₃C₂T_<i>x</i>-PEG) was developed to enhance charge carrier separation and alleviate tumor hypoxia. By incorporating titanium oxide with oxygen vacancies and platinum single atoms onto Ti₃C₂T_<i>x</i> MXene, we not only improve the charge separation efficiency but also prevent the recombination of positive and negative charges generated by the thermoelectric effect, leading to an increased production of reactive oxygen species (ROS). Furthermore, the Pt SAs exhibited excellent catalase-mimicking (CAT-mimicking) activity, catalyzing hydrogen peroxide to generate oxygen and alleviating the hypoxic tumor microenvironment. Titanium oxide with oxygen vacancies also serves as a sonosensitizer for sonodynamic therapy (SDT), enhancing ROS generation in collaboration with thermoelectric catalytic therapy. Moreover, the photothermal conversion efficiency of Pt-TiO_2-<i>x</i>/Ti₃C₂T_<i>x</i>-PEG is augmented by Pt SAs with a surface plasmon resonance effect, further boosting CAT-mimicking activity and thermoelectric catalytic therapy efficacy. This tumor-specific thermoelectric heterojunction integrates thermoelectric therapy, SDT, and photothermal therapy, demonstrating excellent tumor suppression efficacy both in vitro and in vivo. Therefore, this study offers highly valuable and promising insights into utilizing photothermoelectric/ultrasound-mediated methods for cancer treatment.