Activatable photoacoustic contrast agents for sensing and delivering nitric oxide, and development of small molecule photoacoustic platforms with improved properties for in vivo imaging

Molecular imaging is a rapidly expanding and highly interdisciplinary field which strives to visualize and (ideally) quantify chemical and biological processes in living systems. Fortunately, the accessibility of microscopy instrumentation, the commercial availability of a variety of fluorescent dyes, and a thorough understanding of the principles that affect the photophysical properties of these molecules, has facilitated the widespread utilization of fluorescence imaging to scientists of all backgrounds. However, fluorescence imaging is just one of many powerful molecular imaging techniques and is most optimal for studies in cell culture; other methods, including photoacoustic imaging (PAI), ultrasound (US), magnetic resonance imaging (MRI), and positron emission tomography (PET), each provide unique capabilities and can be used effectively at diverse length scales. In the Chan group, we are particularly interested in PAI due to the great potential for high resolution imaging in small animals for preclinical research. As a result, in this document, I briefly discuss the principle of the photoacoustic effect and introduce the basics of photoacoustic tomography (Chapter 1). I then discuss our group’s work to develop near-infrared, ratiometric photoacoustic probes for nitric oxide, with a focus on my contributions to the synthesis and in vivo studies (Chapter 2), as well as my work toward the synthesis and validation of our near-infrared photoactivatable nitric oxide releasing molecules (Chapter 3). I then present a survey of my work to optimize the ratiometric properties of the aza-BODIPY scaffold using conformational restriction (Chapter 4), which represents the first study to investigate the link between structure and ratiometric signal output, followed by my work towards water-soluble congeners that is currently ongoing (Chapter 5). I finish with an introduction to my efforts toward photoacoustic analyte-responsive probes in the second near infrared window, which are also currently underway in our group (Chapter 6). In each chapter, I illustrate the utility of these tools for molecular imaging and highlight our contributions to advancing the field. However, it is important to keep in mind that the full utility of these tools may extend far beyond what is demonstrated here. While my work has focused on the design, optimization, and validation of selective and bioavailable contrast agents, a sustained collaboration between engineers, physicists, chemists, and biologists will be required to improve available PA instrumentation and to design and implement disease models to continue pushing the boundaries of this molecular imaging modality.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2020

Author dc:creator

• Zhou, Effie Yingfei

Contributors dc:contributor

• Chan, Jefferson
• Hergenrother, Paul
• Mitchell, Douglas
• Sarlah, David

• photoacoustic imaging
• small molecule
• contrast agent
• activatable probes
• smart probes
• nitric oxide
• photorelease
• photoactivation
• conformational restriction
• near infrared

Statement dc:rights

• Copyright 2020 Effie Zhou

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/108605

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/108605