Dual-locked small-molecule fluorescent probes for bioimaging and diagnosis

Abstract

Reactive species typically remain at steady-state concentrations within the physiological microenvironment. Disruption of this equilibrium, abnormal upregulation of reactive species and changes in microenvironmental parameters are closely associated with diverse pathological processes. However, these variations of reactive species and microenvironmental parameters are subtle and difficult to detect directly in many pathological contexts. To overcome this limitation, fluorescence imaging technology has emerged as a powerful platform, enabling non-invasive, in situ, real-time visualization of biomolecules and microenvironmental parameters, and providing a sensitive, reliable approach for biomarker detection and disease diagnosis. Within this purpose, small-molecule fluorescent probes have been widely developed and applied in living systems. Compared with single-locked fluorescent probes, dual-locked fluorescent probes can simultaneously detect two distinct biomarkers, thereby enhancing the specificity of monitoring biological events under pathological conditions. In this review, we summarized design strategies, recognition principles, and optical signaling mechanisms of dual-locked small-molecule fluorescent probes, and highlighted representative applications in biosensing, diagnosis, and therapy. Finally, we also discussed current challenges and future directions for their development and proposed corresponding clinical transformation suggustions. © 2024