Syntheses of biocompatible luminescent nanocrystals for visible and short-wave infrared imaging applications

Abstract

The primary focus of this thesis is to synthesize biocompatible luminescent nanocrystals for visible and short-wave infrared (1-2 [mu]m, SWIR) imaging applications. Quantum dots (QDs) have been promising fluorescent probes for biomedical imaging due to their high quantum yield (QY), narrow photoluminescence spectra, and excellent photostability. However, challenges remain to be solved to transfer the as-synthesized hydrophobic QD to aqueous solutions while maintaining the high QY and a compact size. This study involves the design and synthesis of a novel ligand that can be introduced to the established QD synthesis, producing norbornene functionalized QDs that can be readily phase transferred into water via norbornene/tetrazine click chemistry, meanwhile allowing flexible functionalization of the QDs by incorporating a functional group on the hydrophilic chain. This ligand system can be applied to a variety of carboxylic-ligand-stabilized QDs, with emission spectra spanning the visible and the SWIR region. The resulting water-soluble QDs exhibit a high QY, a small hydrodynamic diameter (HD), and excellent colloidal stability and pH stability. Further in vitro cell labeling experiments using azido-functionalized QDs demonstrates their potential for cell targeting applications. As in vivo imaging in the SWIR range has further reduced background noise from tissue scattering compared to traditional visible and near infrared (0.7-1 tm, NIR) imaging, images of higher contrast and better resolution can be readily obtained. The next challenge is to develop SWIR emitters that have high quantum efficiency and minimal toxicity, which is of critical importance in order to promote this technology for clinical applications. Our study found that the emission of luminescent gold nanoclusters can be tuned from the visible to the SWIR region by proper selection of ligands and post ligand modifications. The SWIR-emitting gold nanoclusters have a good QY, a HD that is small enough that they exhibit a rapid renal clearance, and images taken in the SWIR region show better resolution of the blood vessels than in the NIR region.