Recent progress of enzyme-activated small-molecule fluorescent probes in biological systems

Abstract

Enzymes are specialized biological macromolecules with catalytic functions that play crucial roles in supporting normal physiological activities. Dysregulated enzyme activity is directly connected with the onset and progression of numerous diseases. To investigate their distribution, expression levels, and underlying mechanisms of enzyme in living organisms, developing a credible strategy method for detecting enzyme activity is momentous. Fortunately, small-molecule fluorescent probes demonstrated significant advantages in the detection of enzyme activity, including high sensitivity, satisfactory biocompatibility, in suit and real-time detection. Moreover, based on the easy modifying their structures, small-molecule fluorescent probes can meet various needs for monitoring enzyme fluctuations in living systems, facilitating the exploration of its physiological function in specific diseases, providing vital information for personalized therapy. Therefore, this review aims to summarize the design strategies, identification principles, applications, and pathophysiological mechanisms of representative enzyme-activatable small-molecule fluorescent probes. Our ultimate goal is conduced to prepare high-quality fluorescent probes, which are served as powerful tools for the early warning and therapy of certain diseases. © 2025 Elsevier B.V.