Web Release Date: October 25,
Long-Circulating Near-Infrared Fluorescence Core-Cross-Linked Polymeric Micelles: Synthesis, Characterization, and Dual Nuclear/Optical Imaging
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and
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
Received May 16, 2007
Revised August 16, 2007
Abstract:
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,
= 1.25 h; t1/2,
= 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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