NIR-II bioimaging of small molecule fluorophores: From basic research to clinical applications

Due to the low autofluorescence and deep-photo penetration, the second near-infrared region fluorescence imaging technology (NIR-II, 1000-2000 nm) has been widely utilized in basic scientific research and preclinical practice throughout the past decade. The most attractive candidates for clinical translation are organic NIR-II fluorophores with a small-molecule framework, owing to their low toxicity, high synthetic repeatability, and simplicity of chemical modification. In order to enhance the translation of small molecule applications in NIR-II bioimaging, NIR-II fluorescence imaging technology has evolved from its usage in cells to the diagnosis of diseases in large animals and even humans. Although several examples of NIR-II fluorescence imaging have been used in preclinical studies, there are still many challenges that need to be addressed before they can finally be used in clinical settings. In this paper, we reviewed the evolution of the chemical structures and photophysical properties of small-molecule fluorophores, with an emphasis on their biomedical applications ranging from small animals to humans. We also explored the potential of small-molecule fluorophores.