Single-atom catalysts for nano-catalytic tumor therapy: atomic-scale mechanisms in sono-photodynamic therapy

Single-atom catalysts (SACs) have emerged as a powerful class of nano-catalysts for tumor therapy due to their well-defined active sites and exceptional catalytic efficiency. Unlike nanoparticle- or cluster-based systems, SACs exhibit unique electronic structures that facilitate efficient charge separation and the selective generation of reactive oxygen species (ROS) under external stimuli. In this review, we focus exclusively on experimentally verified SAC systems applied in nano-catalytic tumor therapy and sono-photodynamic therapy (SPDT). We systematically discuss the atomic-scale mechanisms by which SACs promote electron–hole separation, catalyse Fenton-like reactions, regulate the tumour microenvironment, and enhance ROS production under both light and ultrasound irradiation. Recent advances in SAC-based photodynamic, sonodynamic, and combined SPDT platforms are critically analysed, with emphasis on structure–activity relationships and catalytic pathways unique to single-atom sites. Finally, current challenges and future directions for translational SAC-based cancer nanomedicine are discussed.