Rational Design of a Small Molecular Near-Infrared Fluorophore for Improved In Vivo Fluorescence Imaging

The near-infrared (NIR) fluorescence imaging modality has great potential for application in biomedical imaging research owing to its unique characteristics, such as low tissue autofluorescence and noninvasive visualization with high spatial resolution. Although a variety of NIR fluorophores are continuously reported, the commercially available NIR fluorophores are still limited, owing to complex synthetic processes and poor physicochemical properties. To address this issue, a small molecular NIR fluorophore (SMF800) was designed and developed in the present work to improve in vivo target-specific fluorescence imaging. After conjugation with pamidronate (PAM) and bovine serum albumin (BSA), the SMF800 conjugates exhibited successful in vivo targeting in bone and tumor tissues with low background uptake, respectively. The improved in vivo performance of the SMF800 conjugate demonstrated that the small molecular NIR fluorophore SMF800 can be widely used in a much broader range of imaging applications. The structure of SMF800, which was developed by considering two important physicochemical properties, water solubility and conjugatability, is first introduced. Therefore, this work suggests a simple and rational approach to design small, hydrophilic, and conjugatable NIR fluorophores for targeted bioimaging.