Molecularly imprinted polymer-integrated nanozymes for biosensing: advances and prospects

Nanozymes engineered nanomaterials with enzyme-like catalytic activity-have emerged as cost-effective and stable alternatives to enzymes. However, their broad substrate range and lack of specificity limit their utility in precision biosensing. To overcome this, molecularly imprinted polymers (MIP) have been integrated with nanozymes, forming hybrid nanozyme@MIP systems that combine catalytic efficiency with molecular recognition. These materials exhibit enhanced selectivity and sensitivity, enabling their application in diverse biosensing platforms, including colorimetric, fluorescence, and electrochemical assays for the detection of drugs, pollutants, and disease biomarkers. This review critically examines recent advances in the design, synthesis, and application of nanozyme@MIP composites. This review provides a timely and comprehensive analysis of molecularly imprinted nanozymes, presenting a viable alternative to conventional enzyme-based systems. It bridges a critical gap by detailing design strategies, catalytic mechanisms, and biosensing applications. Its clarity, depth, and interdisciplinary relevance make it a valuable resource for advancing research and practical applications in this emerging field. We explore various imprinting strategies, catalytic mechanisms, and assay formats, while highlighting their advantages over conventional biosensors, such as improved stability, reusability, and cost-effectiveness. Key challenges are addressed, including the trade-off between selectivity and catalytic activity, non-specific adsorption, and the predominance of peroxidase-like mechanisms. Special attention is given to performance in complex matrices, scalability of synthesis, long-term stability, and biocompatibility. Furthermore, we discuss the need for standardized protocols to ensure reproducibility and comparability across studies and propose design principles to optimize MIP layer properties for enhanced performance. By integrating recent literature and comparative analyses, this review provides a comprehensive framework to guide future research and industrial translation of nanozyme@MIP-based biosensors for diagnostics, environmental monitoring, and point-of-care applications.