Hierarchical electron transfer cascade in POM@MIL-100(Fe)/C3N4 ternary nanozyme: a versatile platform for GSH sensing and tumor redox modulation

Three-level ET cascade relieves bottleneck. • TMB: 5.8x act., 24.2x eff.. • GSH sensing + redox disruption (depletion/ROS). Nanozyme efficiency is fundamentally constrained by interfacial electron transfer (ET) bottlenecks, yet most strategies overlook the rational design of ET pathways. Herein, a ternary NiMo 6 @MIL-100(Fe)/g-C 3 N 4 nanozyme featuring a hierarchical three-level ET cascade was reported: TMB substrates are preconcentrated onto g-C 3 N 4 via π–π stacking (Level I); electrons transfer from g-C 3 N 4 to Fe 3+ nodes of MIL-100(Fe) through interfacial Fe O C bonds (Level II); and finally cascade into the encapsulated NiMo 6 cluster for H 2 O 2 activation and •OH generation (Level III). This design yields higher activity than binary (1.8-fold) and pristine counterparts (5.8-fold), with a 24.2-fold enhancement in catalytic efficiency for TMB. By leveraging glutathione (GSH) as a specific electron cascade interceptor, a colorimetric assay achieves a detection limit of 0.36 μM with excellent selectivity over structurally similar thiols. Beyond sensing, the same cascade efficiently depletes GSH and induces intracellular ROS bursts in HepG2 cells, disrupting tumor redox homeostasis and highlighting its therapeutic potential and establishing a mechanism-driven paradigm for biosensing and cancer therapy. A hierarchical three-level ET cascade transforms electron bottlenecks into a superhighway for GSH sensing and tumor redox therapy. Download: Download high-res image (274KB) Download: Download full-size image