Near-Infrared-II Fluorescent Probes for Analytical Applications: From In Vitro Detection to In Vivo Imaging Monitoring

Biomarkers play a vital role in the regulation of life processes, especially in predicting the occurrence and development of diseases. For the early diagnosis and precise treatment of diseases, it has become necessary and significant to detect biomarkers with sensitivity, accuracy, simplicity, convenience, and even visualization. Fluorescent-probe-based techniques have been recognized as one of the most powerful tools for the sensitive detection and real time imaging of biomarkers in biological samples. However, traditional optical probes, mainly including the visible probes (400-700 nm) and the near-infrared I (NIR-I, 700-900 nm) probes, suffer from low sensitivity, poor resolution, strong absorption and scattering, and high background fluorescence, which hinder effective monitoring of biomarkers. Fortunately, the past decade has witnessed a remarkable evolution in the application fields of near-infrared II (NIR-II, 900-1700 nm) fluorescence, driven by its exceptional optical characteristics and the advancement of imaging technologies. Leveraging the superior penetration capabilities, negligible autofluorescence, and extended fluorescence emission wavelengths, NIR-II fluorescent probes significantly enhance the signal-to-noise ratio (SNR) of in vitro detection (IVD) and the temporal resolution of in vivo imaging. Our team has been committed to the design strategy, controlled synthesis, luminous mechanisms, and biomedical applications of NIR-II fluorescent probes. In this Account, we present the representative works in recent years from our group in the field of NIR-II fluorescent probes for analytical applications, ranging from in vitro detection of biomarkers to in vivo imaging monitoring of different biomarkers and various diseases, which also will further provide a general overview of analytical applications of NIR-II fluorescence probes. First, the in vitro analytical applications of NIR-II fluorescent probes are fully summarized, including tumor marker detection, virus and bacteria analysis, cell testing, and small-molecule sensing. Second, the in vivo imaging monitoring applications of NIR-II fluorescent probes are adequately discussed, including ROS detection, gas monitoring, pH sensing, small-molecule testing, receptor analysis, and the imaging diagnosis of some serious diseases. Finally, we further outline the application advantages of NIR-II fluorescent probes in analytical fields and also discuss in detail some challenges as well as their future development. There is a reasonable prospect that the in vitro detection technology and the in vivo imaging monitoring technology based on NIR-II fluorescent probes will exhibit great development potential in biomedical research and clinical disease diagnosis. We hope that this Account can expand their reach into an even broader spectrum of fields, further enhancing their impact on scientific discovery and medical practice.