Visualizing deeper into the body with a NIR-II small-molecule fluorophore

Abstract

Fluorescence imaging in the near-infrared (NIR) window (750–900 nm) is one of the most popular work modes in biomedical sciences and clinical procedures for visualization of cells and tissues. Up to date, only indocyanine green (ICG) and methylene blue have been approved by the FDA due to their low toxicity and rapid excretion from the body. Although their imaging quality is much more superior than that by visible wavelengths in accurate real-time tumor delineation, the penetration depth of emitted light in biological tissues is still limited. It has recently come to light that even better images can be achieved using fluorophores emitting within the second near-infrared window (NIR-II; 1000–1700 nm). The benefits of NIR-II fluorophores include diminished tissue autofluorescence, reduced photon scattering, and low levels of photon absorption which allows for micron-scale resolution of deep anatomic features. The problem is, however, that most existing NIR-II fluorophores are made from inorganic nanomaterials, such as single-walled carbon nanotubes (SWNTs) and quantum dots. These materials are excreted slowly from the body, and raise concerns about long-term toxicity because they can be retained within the reticuloendothelial system like the liver and spleen. Very recently, a team of researchers led by Xuechuan Hong at Wuhan University, and Zhen Cheng and Hongjie Dai at Stanford University have reported the first smallmolecule fluorescent dye CH1055 for NIR-II imaging (Figure 1) [1]. CH1055 dye (969 Da) having four carboxyl groups absorbs light at ~750 nm and fluoresces at ~1055 nm which can be integrated with a variety of biomolecules for blood and lymphatic vasculatures, tumors and lymph nodes imaging in mice and rats. PEGylation and anti-EGFR affibody conjugation of the dye within the size limit of 40 kDa can be efficiently excreted by kidneys. Indeed, 90% of