Mitochondria-Targeting Bismuth Selenide Nanoparticles for X-ray CT Imaging and Cancer Radiotherapy

Abstract

Abstract Radiotherapy plays an indispensable role in clinical cancer treatment. Designing dual-modal agents for computed tomography (CT) imaging and radiotherapy sensitization remains a great challenge in tumor therapy. In this study, we designed and synthesized bismuth-based nanomaterials (Bi2Se3-TPP, TPP refers to triphenylphosphonium) with mitochondria-preferential accumulation and favorable CT imaging performance and prominent glutathione peroxidase (GPx)-like catalytic activity. The obtained Bi2Se3-TPP can efficiently catalyze the reaction between H2O2 and glutathione (GSH), which induces intracellular GSH depletion and disrupts cellular antioxidant defense. Compared to Bi2Se3-PEG, Bi2Se3-TPP exhibited superior radiosensitization efficiency due to its mitochondrial targeting capability and impaired cellular reactive oxygen species (ROS)-scavenging ability, which facilitates ROS accumulation upon irradiation enhanced ROS generation capacity. In vivo studies demonstrated that Bi2Se3-TPP possessed good biocompatibility, achieving a tumor suppression rate of up to 82.6% in the synergistic treatment group, indicating significant potential for tumor diagnosis and therapy.