Harnessing thermo-hydrogen coupling with palladium hydride nanoparticles for superior antitumor therapy

Photothermal nanomaterials have gained significant attention in cancer treatment due to their excellent photothermal conversion properties. However, photothermal therapy alone often results in incomplete tumor ablation. To improve therapeutic efficacy, we introduce a thermo-hydrogen coupled strategy using palladium hydride (PdH) nanoparticles that combine photothermal heating with hydrogen-driven oxidative stress modulation. PdH nanoparticles were synthesized via a chemical method and systematically characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), UV-Vis spectrophotometry, and thermos response measurements. The results demonstrated that PdH nanoparticles possess small size, high structural stability, good dispersibility, and a photothermal conversion efficiency of 61.9% at 100 µg mL^-1. Hydrogen release upon 532 nm laser irradiation was confirmed using methylene blue decolorization. In vitro studies demonstrated that under laser irradiation, PdH nanoparticles efficiently and stably released hydrogen, enhancing intracellular oxidative stress and leading to selective apoptosis in liver cancer cells while sparing normal liver cells. This effect resulted in an 82% cancer cell death rate, significantly surpassing that of Pd nanoparticles without hydrogen. These findings highlight the mechanistic advantage of thermo-hydrogen synergy and support PdH nanoparticles as a promising platform for controlled and selective cancer therapy.