Leveraging SiO2-Infused COFs for PhotoPyro.

The therapeutic promise of covalent organic frameworks (COFs) in phototheranostic applications has attracted significant attention due to their tunable porosity and design flexibility. However, their clinical translation remains limited by chemical instability and insufficient performance under physiological conditions. To address these issues, we adopted a post-synthetic modification (PSM) strategy, coating SiO2 nanoparticles with ultrathin COF layers through Schiff-base condensation of TAPP and PDCA. This core-shell architecture provides stable and uniform particles while enabling precise incorporation of catalytic sites. As a result, the SiO2@COF platform markedly enhances photocatalytic NADH oxidation, with a turnover frequency (TOF) increase from 8.75 to 43.67 min-1 under normoxia and from 10.3 to 46.7 min-1 even under hypoxia, demonstrating its robust and oxygen-independent catalytic efficiency. Furthermore, the system promotes efficient reactive oxygen species (ROS) generation, activates the caspase-3/GSDME pathway, leading to photon-controlled pyroptosis activation and a significant amplification of therapeutic efficacy. Overall, this metal-free SiO2@COF nanoplatform combines rational design with enhanced catalytic activity and precise biological control, representing a promising advance toward next-generation precision phototherapies.