Synthesis and characterization of a glutathione-responsive NIR-II fluorescent probe with Fenton-like reaction activity.

Stimuli-responsive second near-infrared (NIR-II) fluorescent probes hold substantial promise for precision tumor imaging; however, their translational potential is often constrained by labor-intensive synthetic procedures and insufficient tumor selectivity. Here, we developed three glutathione (GSH)-responsive theranostic nanoprobes using a facile bovine serum albumin (BSA)-templated biomineralization approach, in which BSA-stabilized gold nanoclusters (AuNCs) served as the NIR-II emissive core. The resulting nanoprobes were designated manganese oxide-based AuNCs-MnO2 nanoparticles (NPs), iron oxide-based AuNCs-Fe3O4 NPs, and copper oxide-based AuNCs-CuO NPs. We systematically characterized and compared their microstructures, GSH-triggered fluorescence responses, and catalytic activities toward Fenton-like reactions. Comprehensive analyses demonstrated that, relative to AuNCs-Fe3O4 and AuNCs-CuO NPs, AuNCs-MnO2 exhibited a well-defined spherical architecture with superior monodispersity. Under tumor-relevant GSH concentrations, AuNCs-MnO2 rapidly disassembled, leading to pronounced restoration of the NIR-II fluorescence signal; concurrently, the liberated Mn2+ ions effectively promoted hydroxyl radical (˙OH) production via a Fenton-like process, yielding markedly enhanced theranostic performance compared with the other two formulations. In vitro cellular evaluations and in vivo imaging experiments further substantiated the excellent biocompatibility and strong GSH responsiveness of AuNCs-MnO2 NPs, enabling efficient tumor accumulation, activatable NIR-II fluorescence imaging, and potent chemodynamic therapy (CDT). Collectively, this study provides systematic experimental evidence and a rational design framework for constructing tumor microenvironment (TME)-responsive theranostic nanoplatforms.