Nanozyme-augmented electrochemical biosensors for ultra-sensitive detection of early-stage cancer biomarkers: Recent advances and engineering perspectives

Early cancer screening has become a critical global public health priority and necessitates highly sensitive, specific, and field-deployable bioassay technologies. Electrochemical biosensors (EBs) have shown considerable promise for cancer biomarker analysis due to their high sensitivity, rapid response, and portability, yet their clinical translation remains constrained by insufficient signal amplification and nonspecific interference in complex biological matrices. Nanozymes have emerged as a powerful solution to these challenges. This review provides an engineering-oriented framework that integrates nanozyme catalytic mechanisms with electrode design, signal transduction, and system-level integration. We examine representative applications across five biomarker categories (proteins, nucleic acids, metabolites, circulating tumor cells (CTCs), and exosomes), and highlight how detection strategies diverge fundamentally among affinity-based recognition, programmable nucleic acid amplification, direct catalytic sensing, and cell-capture formats. Key signal amplification paradigms are systematically analyzed, including direct substrate conversion, cascade systems combining nanozymes with natural enzymes or nucleic acid circuits, and relay amplification via redox mediators. We further identify persistent barriers to clinical adoption, such as batch-to-batch reproducibility, specificity in complex biological fluids, and inadequate clinical validation, and discuss engineering countermeasures from material functionalization and device integration perspectives. Finally, we outline future directions toward intelligent microsystems, wearable sensing platforms, and system integration. Collectively, this review offers a systematic engineering blueprint for transitioning nanozyme-enhanced EBs from laboratory research toward clinical cancer diagnostics.