Cu₂O/CuVO₃ Nano-Heterojunction as a Highly Active Therapeutic Catalyst for Aggravating Redox Dyshomeostasis of...

Redox dyshomeostasis is both a hallmark and a vulnerability of cancer cells, offering multiple avenues for therapeutic intervention. Herein, a belt-like nano-heterojunction Cu₂O/CuVO₃ (CVO) is developed as a potential redox dyshomeostasis inducer by exacerbating ROS levels and compromising antioxidant defense without the need of exogenous stimulations. Steady-state analysis reveals that CVO exhibits extraordinary reaction velocity and catalytic efficiency (V_max = 2.32 µm s^-1, K_cat = 0.49 s^-1) in the production of hydroxyl radicals (·OH). Likewise, density functional theory (DFT) calculations indicate that the superb charge-transferring properties in the heterojunction structure and unique surface coverage rate of CVO primarily dominate the high-efficient catalytic reactions. Noteworthy, CVO is capable of inducing mitochondria dysfunction by aggravating the cellular redox imbalance, thereby triggering multiple cell death pathways and generating synergistic effects. Transcriptomics analysis outcomes further demonstrate that CVO exerts significant and distinct effects on key biological processes in tumor cells, encompassing but not limited to canonical pathways such as apoptosis, ferroptosis, and cuprotosis. Both in vitro and in vivo studies demonstrate the pronounced tumor-inhibitory efficacy of CVO, which paves a promising pathway for the development of novel nanocatalysts that effectively target cancer through the amplification of redox dyshomeostasis.