TY - JOUR
T1 - In vivo angiogenesis imaging of solid tumors by αvβ 3-targeted, dual-modality micellar nanoprobes
AU - Kessinger, Chase W.
AU - Khemtong, Chalermchai
AU - Togao, Osamu
AU - Takahashi, Masaya
AU - Sumer, Baran D.
AU - Gao, Jinming
N1 - Funding Information:
We thank the National Institutes of Health (EB005394 and CA129011) for grant support to JG. CK was supported by a DOD Breast Cancer Research Program Multidisciplinary Postdoctoral Fellowship (W81XWH-06-1-07751). This is CSCN000 from the Programs in Cell Stress and Cancer Nanomedicine, Harold C Simmons Comprehensive Cancer Center, UT Southwestern Medical Center at Dallas.
PY - 2010/8
Y1 - 2010/8
N2 - The objective of this study was to develop and evaluate an αvβ3-specific nanoprobe consisting of fluorescent superparamagnetic polymeric micelles (FSPPM) for in vivo imaging of tumor angiogenesis. Spherical micelles were produced using poly(ethylene glycol)-b-poly(D,L-lactide) co-polymers conjugated with tetramethylrhodamine, a fluorescent dye, and loaded with superparamagnetic iron oxide nanoparticles. The resulting micelle diameter was 50-70 nm by dynamic light scattering and transmission electron microscopy measurements. Micelles were encoded with an αvβ3-specific peptide, cyclic RGDfK, and optimized for maximum fluorescence and targeting in αvβ 3-overexpressing cells in vitro. In mice, cRGD-FSPPM-treated animals showed αvβ3-specific FSPPM accumulation in human lung cancer subcutaneous tumor xenografts. Together with the histological validation, the three-dimensional gradient echo magnetic resonance imaging (MRI) data provide high spatial resolution mapping and quantification of angiogenic vasculature in an animal tumor model using targeted, ultrasensitive MRI nanoprobes.
AB - The objective of this study was to develop and evaluate an αvβ3-specific nanoprobe consisting of fluorescent superparamagnetic polymeric micelles (FSPPM) for in vivo imaging of tumor angiogenesis. Spherical micelles were produced using poly(ethylene glycol)-b-poly(D,L-lactide) co-polymers conjugated with tetramethylrhodamine, a fluorescent dye, and loaded with superparamagnetic iron oxide nanoparticles. The resulting micelle diameter was 50-70 nm by dynamic light scattering and transmission electron microscopy measurements. Micelles were encoded with an αvβ3-specific peptide, cyclic RGDfK, and optimized for maximum fluorescence and targeting in αvβ 3-overexpressing cells in vitro. In mice, cRGD-FSPPM-treated animals showed αvβ3-specific FSPPM accumulation in human lung cancer subcutaneous tumor xenografts. Together with the histological validation, the three-dimensional gradient echo magnetic resonance imaging (MRI) data provide high spatial resolution mapping and quantification of angiogenic vasculature in an animal tumor model using targeted, ultrasensitive MRI nanoprobes.
KW - Cancer molecular imaging
KW - Fluorescent polymeric micelles
KW - Magnetic resonance imaging
KW - Superparamagnetic iron oxide
KW - αβ integrin
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U2 - 10.1258/ebm.2010.010096
DO - 10.1258/ebm.2010.010096
M3 - Article
C2 - 20660096
AN - SCOPUS:77955677156
SN - 1535-3702
VL - 235
SP - 957
EP - 965
JO - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)
JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)
IS - 8
ER -