Bimetallic nanozymes and aptamers: A formidable combination for advanced biosensing platforms

Bimetallic nanozymes integrated with aptamers have emerged as a promising platform in biosensing, combining the superior catalytic performance of dual-metal nanostructures with the exquisite molecular recognition of aptamers. The synergistic interplay between two metal components enhances catalytic efficiency, electron transfer, and structural stability beyond that of monometallic nanozymes. Coupled with aptamers, these systems enable rapid, accurate, and cost-effective detection of diverse analytes in complex matrices. This review delineates the fundamental catalytic mechanisms of bimetallic nanozymes alongside principles of aptamer-based target recognition. Key design considerations, including nanozyme composition, metal-organic framework engineering, aptamer selection and immobilization, and strategies for modulating catalytic activity, are critically examined. Diverse signal transduction modalities-colorimetric, fluorescence, electrochemical, and photoelectrochemical-are compared for sensitivity, selectivity, and practicality. The applications of these sensing systems are then summarized across antibiotics, toxins, disease biomarkers, cells, exosomes and microorganisms with emphasis on analytical performance in real samples. Persistent challenges, including limited biocompatibility, aptamer degradation, physiological instability, and fabrication complexity, are highlighted. Future directions emphasize dual-mode and multiplexed sensing, nuclease-resistant aptamer engineering, antifouling surface modifications, simplified assay formats, and rigorous large-scale validation. Collectively, this review provides a framework to guide the rational design and clinical translation of bimetallic nanozyme-aptamer biosensors.