Protein triggered fluorescence switching of near-infrared emitting nanoparticles for contrast-enhanced imaging

Sub-100 nm colloidal particles which are surface-functionalized with multiple environmentally-sensitive moieties have the potential to combine imaging, early detection, and the treatment of cancer with a single type of long-circulating nanodevice. Deep tissue imaging is achievable through the development of particles which are surface-modified with fluorophores that operate in the near-infrared (NIR) spectrum and where the fluorophore's signal can be maximized by turning-on the fluorescence only in the targeted tissue. We present a general approach for the synthesis of NIR emitting nanoparticles that exhibit a protein triggered activation/deactivation of the emission. Dispersing the particles into an aqueous solution, such as phosphate buffered saline (PBS), resulted in an aggregation of the hydrophobic fluorophores and a cessation of emission. The emission can be reinstated, or activated, by the conversion of the surface-attached fluorophores from an aggregate to a monomeric species with the addition of an albumin. This activated probe can be deactivated and returned to a quenched state by a simple tryptic digestion of the albumin. The methodology for emission switching offers a path to maximize the signal from the typically weak quantum yield inherent in NIR fluorophores.