A Bifunctional CoFcMOF Nanozyme Enables Dual-Mode PEC-Colorimetric Immunosensing of C-Reactive Protein with Built-In Cross-Validation

C-reactive protein (CRP), a key inflammatory biomarker, plays a critical role in clinical diagnostics; however, its reliable quantification demands analytical methods that surpass the limitations of conventional single-mode detection by integrating high sensitivity with built-in signal fidelity. Herein, we report a dual-mode photoelectrochemical (PEC) and colorimetric sensing platform based on bifunctional cobalt–ferrocene metal–organic framework (CoFcMOF) nanoflowers (NFs) for the ultrasensitive detection of CRP. The sensor is constructed on an In 2 O 3 -sensitized CdS heterojunction, which facilitates efficient charge separation and enhanced photocurrent response. The CoFcMOF NFs serve a dual function as both an antibody immobilization matrix and a peroxidase (POD)-mimicking signal transducer. Specific antigen–antibody recognition increases the interfacial electron-transfer resistance, leading to effective quenching of the PEC signal, while the POD-like activity of the CoFcMOF NFs catalyzes the oxidation of TMB, generating a distinct colorimetric readout. This integrated approach combines the advantages of intuitive visual screening and precise PEC quantification, addressing the inherent limitations of single-mode detection systems. The dual-mode platform enables simultaneous signal acquisition and achieves ultralow detection limits of 2.9 pg/mL (PEC) and 7.5 pg/mL (colorimetric) for CRP, which was also applied for CRP detection in serum and synovial fluid samples. This design offers significant synergistic advantages in functional integration, signal amplification, detection reliability, selectivity, and universal applicability, positioning it as a robust tool for the early diagnosis and disease monitoring in inflammatory arthritis and beyond. Beyond its analytical performance, this work introduces a versatile and robust paradigm for dual-mode biosensing and provides design principles for constructing multifunctional nanoarchitectures for next-generation sensing technologies.