In vivo angiogenesis imaging of solid tumors by αvβ3-targeted, dual-modality micellar nanoprobes

Abstract

The objective of this study was to develop and evaluate an αv β3-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 αv β3-specific peptide, cyclic RGDfK, and optimized for maximum fluorescence and targeting in αv β3-overexpressing cells in vitro. In mice, cRGD-FSPPM-treated animals showed αv β3-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.