Functional nucleic acid-based fluorescence imaging for tumor microenvironment monitoring: A review

The tumor microenvironment (TME) refers to the complex ecological system surrounding tumor cells, which is intimately associated with regulating tumor cell growth, invasive behavior, and metastatic capacity. Hence, in situ imaging of related bioactivity with resolution in the TME is critical for early cancer detection and accurate diagnosis. In recent years, fluorescence imaging technology has become a widely used tool in TME research due to its non-invasive nature, high spatiotemporal resolution, and capability for real-time monitoring. Among these advancements, signal probes designed based on functional nucleic acids (FNAs) provide a promising and innovative toolkit for targeted imaging analysis of the TME.

This review provides a comprehensive discussion on the construction of FNA-based biosensors and their advancements in TME monitoring. In this review, we initially provide a systematic summary of the current targeting strategies of FNA-based biosensors for visual monitoring of the TME, focusing on targeting cell surface and extracellular matrix components. Subsequently, we further explore the application of FNA-based biosensors in monitoring the TME. These biosensors have successfully achieved the monitoring of key parameters, bioactive molecules and other tumor markers in the tumor microenvironment due to their excellent molecular recognition ability and high sensitivity. Finally, we discuss some of the challenges currently faced in the field. In response to these challenges, we propose potential research directions and look forward to the future development prospects of this field.

Unlike previous reviews of biosensors based on FNAs for imaging tumor markers in the TME, this work is the first to review how such biosensors can be anchored in the TME. With continued efforts and advancements, we believe an increasing number of FNA-based fluorescence imaging probes will be utilized for TME imaging. This progress will significantly enhance our understanding of disease pathogenesis and progression, thereby offering substantial potential in biosensing and imaging analysis.