In vivo monitoring of tumor distribution of hyaluronan polymeric micelles labeled or loaded with near-infrared fluorescence dye

Abstract

Development of delivery systems which allow real-time visual inspection of tumors is critical for effective therapy. Near-infrared (NIR) fluorophores have a great potential for such an application. To overcome NIR dyes short blood circulation time and increase tumor accumulation, a NIR dye, cypate, was associated with oleyl hyaluronan, which can self-assemble into polymeric aggregates. The cypate association with oleyl hyaluronan was performed either by a covalent linkage, or physical entrapment. The two systems were compared for tumor targeting and contrast enhancement using BALB/c mice bearing 4T1 breast cancer tumors. Independently on the way of cypate association, it took more than 24 h from intravenous administration to detect NIR signal in tumors and the tumors were clearly visualized for 2 following weeks without substrate reinjection. Covalently linked cypate generated 2–3 fold stronger fluorescence signal than physically loaded cypate. This study demonstrates the potential of HA matrix to be used as carrier of contrast agents for non-invasive long-term tumor visualization.