Amorphization-Induced Electronic Modulation of Gd(OH)3 Nanocages with Enhanced Enzymatic Activities for Antitumor Therapy.

In nanotechnology-based cancer therapy, modulating electronic states of nanomaterials is crucial for influencing spatiotemporal dynamic behaviors of intracellular reduction-oxidation and redox homeostasis. Although rare-earth transition metals with 4f electrons present electronic energy levels suitable for electronic modulation, its practical realization is challenging due to strong 4f electron localization. Theoretical studies indicate that amorphization can significantly alter the electronic states of the 4f-dominated nanomaterials. However, the isotropic nature of disordered structures poses challenges for morphology and dimensional regulation of amorphous nanomaterials, which is important in tumor therapy. In this study, we designed and synthesized amorphous Gd(OH)3 nanocages with regulated electronic states for antitumor therapy. The reduction of the Gd-O coordination number in the amorphous structure significantly diversifies the spatial occupancy, alters the electronic states, and enhances hole delocalization, thereby boosting the redox capability of the originally inert Gd3+ compound (half-filled 4f7 orbit). This results in unexpected peroxidase (POD)-like catalytic activity, with a Kcat of 3.49 × 104 s-1, which is an order of magnitude higher than that of the natural HRP enzyme. The amorphous Gd(OH)3 nanocages also show impressive antitumor effects both in vitro and in vivo, demonstrating that amorphization is an effective strategy for modulating the electronic states of rare earth elements and unlocking new catalytic and biomedical potential for advanced synthetic nanozymes.