Tumor cell-on fluorescence imaging agent using hyaluronate dots

We report here the use of near-infrared fluorescent dye-labelled hyaluronate (HA) dot named HDFc for tumor imaging. We took advantage of the unique auto-quenching characteristic that occurs when the fluorescent dye molecules are in close proximity to one another under ordinary conditions. However, when the HDFc is located in tumor cells, the tumor cell-specific enzyme (e.g., hyaluronidase: HAase) affects the structure of the HDFc, followed by the transition from auto-quenched dye molecules to dequenched dye molecules, resulting in the identification of the tumor cells. For this purpose, HDFcs were synthesized, characterized, and exogenously treated with HAase to demonstrate the enzyme-dependent HDFc photoactivity. Specifically, confocal microscopy and flow cytometry confirmed the efficient cellular internalization and fluorescence production of HDFc in CD44+ and HAase-abundant tumor cells. Collectively, this study opens the door for utilizing polymeric dots to visualize tumor cells by introducing biocompatible HA and tumor cell-on photoluminescent dye.