Near-Infrared Dye-Conjugated Amphiphilic Hyaluronic Acid Derivatives as a Dual Contrast Agent for In Vivo Optical and Photoacoustic Tumor Imaging

Amphiphilic hyaluronic acid (HA) derivatives bearing hydrophobic indocyanine green dye derivatives and hydrophilic poly­(ethylene glycol) were synthesized through the use of condensation and copper-catalyzed click cyclization reactions. The amphiphilic HA derivatives dissolved in water and formed self-assemblies in which the near-infrared dyes were tightly packed and arranged to form dimers or H-aggregates. By irradiating an aqueous solution of HA derivatives with near-infrared light, photoacoustic signals were detected along with fluorescence emission. Self-assemblies consisting of HA derivatives could smoothly accumulate in tumor tissues by passive tumor targeting. By utilizing HA derivatives as a contrast agent, tumor sites were clearly visualized by optical imaging as well as by photoacoustic tomography.