Photothermal and ROS-mediated cellular apoptosis using copper-driven Prussian blue analog nanoparticles with bimetallic reaction centres

The development of chemodynamic therapy (CDT) agents derived from copper and iron is crucial due to their ability to their biological safety, biocompatibility, and bio-specificity to only kill cancer cells. This study investigates bimetallic copper/iron-Prussian blue coordination analogs nanoparticles (CuxFey-PBAs, x = 15, 11, 7, 4, 0; y = 0, 4, 8, 11, 15), which exhibit photothermally enhanced bimetallic central catalytic activity for effective cancer treatment. By adjusting the Cu2+/Fe2+ ratio, CuxFey-PBAs demonstrated remarkable photothermal properties (from 1.9 % to 39.75 %) and exceptional reactive oxygen species (ROS) activity (k: 0.077 min−1, R2: 0.97), leading to mitochondrial dysfunction and subsequent tumour cell death. Density functional theory (DFT) calculations highlighted that the most critical factors influencing photothermal properties are carrier concentration and electron transition. The electronic structure of the bimetallic centre was found to significantly correlate with the reaction pathway and ROS activity. In vitro experiments showed that CuxFey-PBAs can enter cancer cells via endocytosis, induce mitochondrial dysfunction, and cause cancer cell death through apoptosis. Compared to conventional ROS-mediated systems, CuxFey-PBAs with photothermal properties exhibit superior ROS catalytic activity, facilitating photothermally enhanced CDT. These findings represent a significant advancement in synergistic photothermal-enhanced Fenton reaction with bimetallic reaction centres, offering a novel strategy for CDT enhancement.