Supramolecular quantum dot-porphyrin assemblies for biological oxygen sensing

Abstract

Generating metabolic profiles of tumors provides a spatiotemporal map of the concentration of key species to assess and quantify tumor growth, metabolism, and response to therapy. Because the tumor microenvironment is characterized by hypoxia, the concentration of oxygen is an important indicator of tumor health. Understanding how this parameter changes as a function of disease progression is critical to develop novel targeted therapeutics. New non-invasive sensors must be developed that are small enough to penetrate into the tumor and monitor dynamic changes with high resolution. To this end, this thesis presents new oxygen sensors that are a supramolecular assemblies of a quantum dot (QD) and a palladium(II) porphyrin. High spectral overlap between QD emission and porphyrin absorption results in efficient Förster resonance energy transfer (FRET) for signal transduction in these sensors. Porphyrins with meso pyridyl substituents bind to the surface of the QD to produce self-assembled nanosensors. Since these macrocycles are sensitive in the 0-160 torr range, they are ideal phosphors for in vivo biological oxygen quantification. The QD serves as a two-photon antenna to enable sensing under two-photon excitation. Multiphoton imaging is a powerful technique that is nondestructive to tissue and provides high-resolution images of live tissue at depths of several hundred microns with submicron spatial resolution. Having studied the photohysical properties of these sensors under both one- and two-photon excitation in organic solvents, these sensors were then encapsulated in lipid micelles to quantify oxygen in aqueous media. In these constructs, the quantum dot also serves as an internal intensity standard, furnishing a ratiometric oxygen sensor. Preliminary in vivo multiphoton imaging and oxygen measurements were conducted using mice with chronic dorsal skinfold chambers or cranial windows. Together, the properties of this sensor establish a ratiometric two-photon oxygen sensor for applications in probing biological microenvironments.