Site-specific albumin tagging with chloride-containing near-infrared cyanine dyes: molecular engineering, mechanism, and imaging applications.

Near-infrared dyes, particularly cyanine dyes, have shown great potential in biomedical imaging due to their deep tissue penetration, high resolution, and minimal tissue autofluorescence/scattering. These dyes can be adjusted in terms of absorption and emission wavelengths by modifying their chemical structures. The current issues with cyanine dyes include aggregation-induced quenching, poor photostability, and short in vivo circulation time. Encapsulating cyanine dyes with albumin, whether exogenous or endogenous, has been proven to be an effective strategy for improving their brightness and pharmacokinetics. In detail, the chloride-containing (Cl-containing) cyanine dyes have been found to selectively bind to albumin to achieve site-specific albumin tagging, resulting in enhanced optical properties and improved biosafety. This feature article provides an overview of the progress in the covalent binding of Cl-containing cyanine dyes with albumin, including molecular engineering methods, binding sites, and the selective binding mechanism. The improved optical properties of cyanine dyes and albumin complexes have led to cutting-edge applications in biological imaging, such as tumor imaging (diagnostics) and imaging-guided surgery.