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Evaluation of Temperature-Sensitive, Indocyanine Green-Encapsulating Micelles for Noninvasive Near-Infrared Tumor Imaging

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ABSTRACT

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.

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ACKNOWLEDGEMENTS

This work was supported by the funds from the Washington Technology Center and Omeros Corporation (Pun and Li), and in part by the National Institutes of Health (Grant No. R01 CA120480-Li). Xenogen Spectrum imaging was conducted through the Center for Intracellular Delivery of Biologics, funded by Washington State Life Sciences Discovery Fund Grant 2496490.

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Author notes

  1. Yongping Chen & Xingde Li

    Present address: Department of Biomedical Engineering, Johns Hopkins University, 720 Rutland Avenue Ross 731B, Baltimore, Maryland, 21205, USA

Authors and Affiliations

  1. Department of Bioengineering, University of Washington, Box 355061, William H. Foege Building, 3720 15th Ave NE, Seattle, Washington, 98195-5061, USA

    Tae Hee Kim, Yongping Chen, Christopher W. Mount, Xingde Li & Suzie H. Pun

  2. Omeros Corporation, 1420 Fifth Avenue, Suite 2600, Seattle, Washington, 98101, USA

    Wayne R. Gombotz

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  1. Tae Hee Kim
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Correspondence to Xingde Li or Suzie H. Pun.

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Kim, T.H., Chen, Y., Mount, C.W. et al. Evaluation of Temperature-Sensitive, Indocyanine Green-Encapsulating Micelles for Noninvasive Near-Infrared Tumor Imaging. Pharm Res 27, 1900–1913 (2010). https://doi.org/10.1007/s11095-010-0190-y

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  • DOI: https://doi.org/10.1007/s11095-010-0190-y

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