Nanozyme-based biosensors with different combinations of sensing modes for clinical biomarker detection: Biosensing strategies, practical applications, and future perspectives

The emergence of precision medicine has significantly highlighted the pivotal role of biomarker detection in disease diagnosis, staging, treatment, and prognosis. However, the low abundance of biomarkers in the early disease stages presents substantial challenges for conventional detection methods. Nanozyme-based biosensing platforms, which are characterized by high sensitivity, operational simplicity, and cost-effectiveness, have emerged as transformative solutions. Recent advances have led to the development of diverse nanozyme-based biosensors employing multiple signal output modes, including colorimetric, fluorescent, and electrochemical sensing. Furthermore, dual-mode and multi-mode sensing strategies have enhanced detection accuracy and reliability by integrating multiple signal outputs, effectively addressing the limitations of single-mode sensing in complex physiological environments and demonstrating superior performance in clinical biomarker detection. This review provides a comprehensive discussion of the principles underlying nanozyme-based biosensors, strategies for integrating different sensing modes, and their applications in clinical biomarker detection. Additionally, we summarize current challenges and future directions for advancing nanozyme-based biosensing technologies. • Biosensing strategies of single-, dual-, and multimode nanozyme-based biosensors with varying combinations are summarized. • Applications of nanozyme-based biosensors with diverse mode combinations for clinical biomarkers detection are summarized. • Current challenges and future directions for advancing nanozyme-based biosensing technologies are discussed.