Construction and optimization of organic fluorophores in NIR-II fluorescence imaging

Second near-infrared fluorescence imaging (NIR-II FLI, 1000-1700 nm) has recently emerged as a cutting-edge imaging modality, offering deeper tissue penetration and superior clarity compared to the visible (400-700 nm) and conventional NIR-I FLI (700-900 nm) due to the reduced photon scattering, weaker tissue autofluorescence, and lower self-absorption. However, the short absorption/emission wavelengths, low fluorescence brightness, and poor biocompatibility of fluorophores remain major obstacles for NIR-II FLI. In contrast to their inorganic counterparts, organic fluorophores (OFs), including cyanine dyes, D-A structured conjugated small molecules, and semiconducting polymers, exhibit tunable optical properties and high biocompatibility, thereby enabling NIR-II FLI for imaging anatomic structures, specific markers, and physiological activities. This review comprehensively summarizes recent progress in NIR-II FLI by highlighting an increasingly developing palette of biocompatible OFs with tunable NIR-II emission wavelengths. Various optimization strategies are emphasized to enhance the performance of OFs in terms of absorption and emission wavelengths, fluorescence quantum yields, and biocompatibility. Furthermore, the diverse applications of OFs in vascular imaging, lymphatic imaging, tumor imaging, organ imaging, imaging-guided therapy, and biosensors are summarized and introduced. Finally, current challenges and future prospects for the clinical translation of OFs are discussed.