Directional interfacial charge transfer in NiFe heterostructure nanozymes for ultrasensitive cancer diagnostics.

Abstract

Translating the extraordinary intrinsic catalytic activity of nanozymes into ultra-sensitive, label-free diagnostic signals remains a fundamental challenge, primarily due to the limited macroscopic current perturbations induced by trace biomolecular binding. Herein, we transcend this limitation by establishing a seamless intrinsic connection between a hyperactive heterostructure nanozyme and a spatial "nanoscale gatekeeping" amplification paradigm. Initially, a hierarchical porous carbon-encapsulated NiFe alloy/oxide nanozyme (ZIF-C@NiFe) was engineered. Within this architecture, an interfacial work-function mismatch establishes a robust built-in electric field. As unambiguously revealed by X-ray photoelectron spectroscopy (XPS), this field drives a directional Ni-to-Fe charge redistribution, enriching surface Ni3+ species and radically accelerating Fe2+/Fe3+ cycling. This interfacial electronic modulation generates an exceptionally high baseline current for Fenton-like H2O2 cleavage. To harness this powerful catalytic "engine" for sensing, capture antibodies were strategically immobilized at the bottlenecks of the ZIF-C hierarchical pores. Upon specific recognition of carcinoembryonic antigen (CEA), the bulky immunocomplexes act as physical molecular valves. This severe diffusion-gating effect abruptly cuts off substrate mass transport to the hyperactive internal active network, translating a trace molecular binding event into a massive macroscopic signal drop (negative cascade amplification). Driven by this synergetic mechanism, the integrated immunosensor achieves a phenomenal limit of detection of 0.05 fg/mL and demonstrates robust diagnostic accuracy in clinical breast cancer serum samples (AUC = 0.974). This work systematically bridges interfacial electronic engineering with diffusion-gated signal transduction, offering a transformative design rationale for next-generation clinical diagnostics.

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