Highly Expressive Bienzyme and Photothermal Effect Co-Enabled by the Co-O-Mn Bridge for Potentiating 1550 nm...

Development of single-atom nanocatalysts with photoresponsive and enzyme-like properties has opened innovative avenues for improving the tumor photodynamic therapy (PDT) effect. However, their further application was restricted by the insufficient adsorption/desorption for multireaction intermediates and poor light tissue penetration. Herein, we constructed mesoporous silica-supported, O-bridged asymmetric cobalt-manganese (Co-O-Mn) dual-atom nanozyme, coated on the surface of 1550 nm-excited upconversion (UC) nanoparticles and modified with polyethylene glycol (denoted as P/U@CoMn_DA), for the PDT, thermal-enhanced enzyme dynamic therapy, and magnetic resonance imaging. Interestingly, the incorporation of Co-O-Mn sites not only selectively enhanced the catalase (CAT)- and oxidase (OXD)-like activities of the P/U@CoMn_DA, but also suppressed the peroxidase-like reaction and endowed the nanocatalysts with a narrowed bandgap (1.25 eV). Experimental and theoretical analyses revealed that the incorporation of Co-O-Mn sites upshifted the d-band center and optimized the adsorption-dissociation equilibrium for the O-containing intermediates. Under the dual stimulation of 1550 nm irradiation and intratumoral acidity, the H₂O₂ substrate was decomposed by CAT-like activity into O₂, which was reduced to ·O₂^- by UC-induced electrons and OXD-like activity, and further oxidized by holes to cytotoxic ¹O₂. Leveraging its high photothermal conversion property (η = 52.8%) and bienzymatic cascade performances, P/U@CoMn_DA exhibited desirable tumor growth inhibition (92.8%). This work established practicable paradigms for designing the biomedical nanozymes at the atomic level.