Liang Zuoxiang, Tian Fengyu
Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou, Fujian, 350122, PR China; Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350122, PR China.
Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou, Fujian, 350122, PR China.
Anal Chim Acta. 2025 May 8;1350:343794. doi: 10.1016/j.aca.2025.343794. Epub 2025 Feb 13.
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.
肿瘤微环境（TME）是指围绕肿瘤细胞的复杂生态系统，与调节肿瘤细胞生长、侵袭行为和转移能力密切相关。因此，在肿瘤微环境中对相关生物活性进行原位成像并具有高分辨率，对于早期癌症检测和准确诊断至关重要。近年来，荧光成像技术因其非侵入性、高时空分辨率和实时监测能力，已成为肿瘤微环境研究中广泛使用的工具。在这些进展中，基于功能性核酸（FNA）设计的信号探针为肿瘤微环境的靶向成像分析提供了一个有前景的创新工具包。
本综述全面讨论了基于FNA的生物传感器的构建及其在肿瘤微环境监测中的进展。在本综述中，我们首先系统总结了基于FNA的生物传感器用于肿瘤微环境可视化监测的当前靶向策略，重点关注靶向细胞表面和细胞外基质成分。随后，我们进一步探讨了基于FNA的生物传感器在监测肿瘤微环境中的应用。由于其出色的分子识别能力和高灵敏度，这些生物传感器已成功实现对肿瘤微环境中关键参数、生物活性分子和其他肿瘤标志物的监测。最后，我们讨论了该领域目前面临的一些挑战。针对这些挑战，我们提出了潜在的研究方向，并展望了该领域的未来发展前景。
与以往关于基于FNA的生物传感器用于肿瘤微环境中肿瘤标志物成像的综述不同，这项工作首次综述了此类生物传感器如何锚定在肿瘤微环境中。随着持续的努力和进展，我们相信越来越多基于FNA的荧光成像探针将用于肿瘤微环境成像。这一进展将显著增强我们对疾病发病机制和进展的理解，从而在生物传感和成像分析中提供巨大潜力。
