Tumor microenvironment-responsive thermoelectric scaffold for on-demand antitumor therapy

Thermoelectric material could realize the thermal-electricity-reactive oxygen species (ROS) conversion under temperature gradient, being considered a promising candidate for tumor therapy. Nevertheless, it required exogenous excitation such as light irradiation, causing difficultity in achieving on-demand therapy. Herein, a tumor microenvironment responsive Bi 2 Te 3 –CaO 2 nanohybrid was synthetized by in situ growing calcium peroxide (CaO 2 ) nanoparticles on thermoelectric bismuth telluride (Bi 2 Te 3 ) nanosheets, and then blended with poly- l -lactic acid (PLLA) to fabricate a PLLA/Bi 2 Te 3 –CaO 2 scaffold. Once the acidic microenvironment of the tumor was sensed, the CaO 2 would serve as an intelligent switch, releasing heat through rapid hydrolysis and triggering the thermoelectrocatalysis of Bi 2 Te 3 to generate ROS, thereby achieving on-demand therapy. Results demonstrated that the scaffold exhibited rapid temperature rise and significant ROS catalytic formation ability in an acidic solution (pH 5.5), while no significant changes occurred in a neutral environment (pH 7.4). Annexin V-FITC/PI staining and JC-1 assay demonstrated that the generated ROS could induce tumor apoptosis by reducing mitochondrial membrane potential. Besides, the fluorescent probe test revealed that CaO 2 could also produce hydrogen peroxide (H 2 O 2 ) and calcium ions (Ca 2+ ) to interfere with intracellular Ca 2+ , thereby further enhancing the antitumor effect. Overall, this work proposed a novel perspective for on-demand antitumor therapy.