Phototherapy ablation of rabbit orthotopic tumors by non-stoichiometric BiPO4-x nanoparticles

Abstract Although near-infrared (NIR)-mediated phototherapy has achieved great progresses, mice with subcutaneous tumors are employed by nearly all previous phototherapy studies, which is largely different from the clinical human tumors. A large animal model with orthotopic carcinoma is highly demanded before clinical practice. This work designs a non-stoichiometric photoactive substance of BiPO4−x for the phototherapy on both of subcutaneous tumor-bearing mice and orthotopic VX2 tumor-bearing rabbit, aiming for perspective clinic prediction. Oxygen defective BiPO4−x is a brand-new phototherapeutic agent with desirable NIR-harvesting properties, which facilitate production of hyperthermia and reactive oxygen species (ROS), and thus contribute to a synergistic photothermal/photodynamic therapy (PTT/PDT) outcome. The photoabsorption mechanism of BiPO4−x predicted by density functional theory reveals the emergence of abundant middle band transition as oxygen defect introduction, accounting for a NIR absorption resultantly. The antitumor evaluation on large animal model of rabbits is realized with ultrasound (US) technique and contrast-enhanced ultrasound (CEUS) for deep orthotopic tumor examination. To be excited, the effective elimination of orthotopic rabbit tumors is successfully achieved. Hence, this work advances tumor phototherapy further to the macroanimal model, which makes it to be more clinically relevant.