Evaluation of temperature-sensitive, indocyanine green-encapsulating micelles for noninvasive near-infrared tumor imaging

Purpose: Indocyanine green (ICG), an FDA-approved near infrared (NIR) dye, has potential application as a contrast agent for tumor detection. Because ICG binds strongly to plasma proteins and exhibits aqueous, photo, and thermal instability, its current applications are largely limited to monitoring blood flow. To address these issues, ICG was encapsulated and stabilized within polymeric micelles formed from the thermo-sensitive block copolymer Pluronic F-127, poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide), to increase the stability and circulation time of ICG. Methods: ICG-loaded Pluronic micelles were prepared at various concentrations of Pluronic and ICG and characterized by determining particle sizes, dye loading efficiency, and the kinetics of dye degradation. Förster resonance energy transfer spectroscopy was employed to monitor the stability of Pluronic micelles in physiological solutions. The plasma clearance kinetics and biodistribution of ICG-loaded micelles was also determined after intravenous delivery to CT-26 colon carcinoma tumor-bearing mice, and NIR whole-body imaging was performed for tumor detection. Results: The Pluronic F-127 micelles showed efficient ICG loading, small size, stabilized ICG fluorescence, and prolonged circulation in vivo. Solid tumors in mice were specifically visualized after intravenous administration of ICG-loaded micelles. Conclusions: These materials are therefore promising formulations for noninvasive NIR tumor imaging applications.