Spatiotemporal-switchable 2D NIR-II single-atom nanozyme for single-cell–level surgical navigation and glioblastoma phototherapy

Single-cell–level resolution tumor therapy represents an advanced strategy against glioblastoma but lacks suitable theranostic agents. Here, we developed a spatiotemporal-switchable, two-dimensional (2D), bismuthene-based second near-infrared window (NIR-II) nanozyme. In this platform, the bismuthene scaffold simultaneously directed the assembly of indocyanine green (ICG) into ordered J -aggregates and anchored monodispersed platinum (Pt) atoms. The resulting J -aggregates acted as an optical antenna with a long-wavelength absorption peak at 895 nanometers and high photobleaching resistance of 78.0%, enabling the identification of single tumor cells with a resolution of 44.3 micrometers at 1350 nanometers for precise glioma resection. Postoperatively, the spatiotemporal-switchable function was activated for therapeutic intervention, in which the photothermal effect amplified the original efficiency of the catalase-like activity of Pt atoms by threefold, driving a surge in intracellular oxygen to combat tumor hypoxia. Upon 808-nanometer irradiation, the induced oxygen release in the tumor microenvironment amplified ICG-mediated photodynamic therapy, and combined with bismuthene-mediated photothermal therapy, it effectively inhibited residual tumors. In an orthotopic glioma mouse model, this approach minimized recurrence and achieved increased survival without inducing neurological or motor deficits. This work provides an atomic-level and molecular-level design blueprint for NIR-II nanotheranostic agents, paving the way toward clinical translation of single-cell–level precision medicine for brain malignancies.