In vivo angiogenesis imaging of solid tumors by alpha(v)beta(3)-targeted, dual-modality micellar nanoprobes.
The objective of this study was to develop and evaluate an alpha(v)beta(3)-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 alpha(v)beta(3)-specific peptide, cyclic RGDfK, and optimized for maximum fluorescence and targeting in alpha(v)beta(3)-overexpressing cells in vitro. In mice, cRGD-FSPPM-treated animals showed alpha(v)beta(3)-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.
Kessinger
Chase W
CW
Department of Pharmacology, Harold C Simmons Comprehensive Cancer Center, Dallas, TX, USA.
Khemtong
Chalermchai
C
Togao
Osamu
O
Takahashi
Masaya
M
Sumer
Baran D
BD
Gao
Jinming
J
D000818:Animals; D005260:Female; D052203:Ferrosoferric Oxide / Q000737:chemistry; D005456:Fluorescent Dyes / Q000032:analysis / Q000737:chemistry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008175:Lung Neoplasms / Q000098:blood supply / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics; D053768:Metal Nanoparticles / Q000032:analysis*; D051379:Mice; D008819:Mice, Nude; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D057054:Molecular Imaging / Q000379:methods*; D009369:Neoplasms / Q000098:blood supply* / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000175:diagnosis; D010456:Peptides, Cyclic / Q000378:metabolism; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry; D012235:Rhodamines / Q000032:analysis / Q000737:chemistry; D012542:Scattering, Radiation; D023041:Xenograft Model Antitumor Assays
D005456:Fluorescent Dyes; D039302:Integrin alphaVbeta3; D008823:Micelles; D010456:Peptides, Cyclic; D011091:Polyesters; D012235:Rhodamines; C099250:cyclic (arginyl-glycyl-aspartyl-phenylalanyl-lysyl); C033616:poly(lactide); C005358:tetramethylrhodamine; D052203:Ferrosoferric Oxide