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Long-Circulating Near-Infrared Fluorescence Core-Cross-Linked Polymeric Micelles:  Synthesis, Characterization, and Dual Nuclear/Optical Imaging

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    Long-Circulating Near-Infrared Fluorescence Core-Cross-Linked Polymeric Micelles:  Synthesis, Characterization, and Dual Nuclear/Optical Imaging
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    Department of Experimental Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, Carestream Health, Inc., 1049 Ridge Road West, Rochester, New York 14615, and Eastman Kodak Company Research Labs, 1999 Lake Avenue #710, Rochester, New York 14650
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    Biomacromolecules

    Cite this: Biomacromolecules 2007, 8, 11, 3422–3428
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    https://doi.org/10.1021/bm7005399
    Published October 25, 2007
    Copyright © 2007 American Chemical Society
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    Abstract

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    We report the synthesis of PEG-coated, core-cross-linked polymeric micelles (CCPMs) derived from an amine-terminated amphiphilic block copolymer, poly(PEG-methacrylate)-b-poly(triethoxysilyl propylmethacrylate). The block copolymer self-assembled to form micellar nanoparticles, and a Cy-7-like near-infrared fluorescence (NIRF) dye was entrapped in the core bearing reactive ethoxysilane functional groups through a subsequent sol−gel process. The fluorescent signal of CCPMs on the molar basis was 16-fold brighter than that of Cy7. With an average diameter of 24 ± 8.9 nm, CCPMs exhibited a prolonged blood half-life (t1/2,α = 1.25 h; t1/2,β = 46.18 h) and moderate uptake by the mononuclear phagocytic system. Significant accumulation of CCPMs in human breast tumor xenografts allowed noninvasive monitoring of the uptake kinetics with both NIRF optical and gamma imaging techniques. Our data suggest that Cy7-entrapped CCPM nanoparticles are suitable for NIRF imaging of solid tumors and have potential applications in the imaging of tumor-associated molecular markers.

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    †

     The University of Texas M. D. Anderson Cancer Center.

    #

     On leave from Department of Nuclear Medicine, Peking University School of Oncology & Beijing Cancer Hospital, Beijing, China 100036.

    §

     Eastman Kodak Company Research Labs.

    ‡

     Carestream Health, Inc.

    *

     Corresponding author. Department of Experimental Diagnostic ImagingUnit 59, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030. Phone:  (713) 792-5182. Fax:  (713) 794-5456. E-mail:  [email protected].

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    (1) Summary of physicochemical properties and pharmacokinetic parameters; (2) TEM photograph and 1H NMR spectrum of PPEGMA-b-PESPMA block copolymer; (3) ITLC analysis of freshly prepared 111In−DTPA−CCPM, 111InCl3, and urine samples. These materials are available free of charge via the Internet at http://pubs.acs.org.

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    Cite this: Biomacromolecules 2007, 8, 11, 3422–3428
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    https://doi.org/10.1021/bm7005399
    Published October 25, 2007
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