pH-triggered Schottky heterojunctions for NIR-II-activated and tumor-specific pyroelectrodynamic and photothermal therapy

Pyroelectrodynamic therapy (PEDT) of tumors faces challenges due to its low electrocatalytic efficiency at mild temperature and the potential for off-target toxicity to healthy tissue. To overcome these issues, we have engineered pyroelectric nanoparticles (NPs) that feature a pH-triggered heterojunction structure and tumor-selective reactive oxidative species (ROS) production, faclitating synergistic PEDT and mild photothermal therapy (PTT). Herein, molybdenum trioxide (MoO 3 ) was deposited in-situ on the surface of tetragonal BaTiO 3 (tBT) to create tBT@MO. Subsequently, a metal-acid treatment was utrilized to hydrogenate MoO 3 , and the yielded HMO was grafted with poly(ethylene glycol) (PEG) to produce tBT@HMO-PEG. In contrast to vulnerability in normal tissues, hydrogen-doped NPs exhibit stability against H + attacks in the slightly acidic microenvironment of tumors, faclitating efficient near-infrared II (NIR-II) absorption, and the enhanced photothermal conversion enables tumor-selective mild PTT and PEDT. The formation of heterojunctions between tBT and HMO markedly improves electron-hole separations and ROS productions, and the generated pyroelectric field selectively disrupts the membrane potentials of tumor cells, theraby promoting NP internalization. In a tumor-bearing model, NPs exhibit deep tumor penetration and widesperead ROS distribution, overcoming the limitations of the short lifespan and diffusion distance of ROS to achieve potent antitumor efficacy. Moreover, the tumor-selective PEDT and mild hyperthermia ensure treatment safety. Therefore, the innovative design of pH-triggered Schottky heterojunctions effectively mitigate off-target toxicity to normal tissue while improving the precision and efficacy of tumor therapy.