Evaluation of temperature-sensitive, indocyanine green-encapsulating micelles for noninvasive near-infrared tumor imaging.
OBJECTIVE
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.
Kim
Tae Hee
TH
Department of Bioengineering, University of Washington, Box 355061, William H. Foege Building, 3720 15th Ave NE, Seattle, Washington 98195-5061, USA.
Chen
Yongping
Y
Mount
Christopher W
CW
Gombotz
Wayne R
WR
Li
Xingde
X
Pun
Suzie H
SH
D000818:Animals; D003287:Contrast Media / Q000737:chemistry* / Q000493:pharmacokinetics; D029721:Drosophila Proteins; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D007208:Indocyanine Green / Q000737:chemistry* / Q000493:pharmacokinetics; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D009369:Neoplasms / Q000175:diagnosis*; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*; D013696:Temperature
D003287:Contrast Media; D029721:Drosophila Proteins; D004337:Drug Carriers; D008823:Micelles; C529564:rudhira protein, Drosophila; D020442:Poloxamer; D007208:Indocyanine Green