Rational design of activity-based sensing probes to reveal the impact of inflammation on human disease progression

Molecular imaging is a powerful tool that has allowed researchers to probe complex biological phenomena. Broadly, molecular imaging relies on the partnership between a detection component and a signaling moiety. In this regard, engagement of the receptor with the target allows for signal output (e.g., light or sound). In the 2000s, the molecular imaging field advanced further with the development of activity-based sensing. This development has permitted the investigation of reactive and fleeting biological species that play important roles in both normal and disease physiology. Prior to the development of activity-based sensing, molecular imaging probes could only provide information on the presence (or absence) of an analyte. Now, tools are being generated in which the activity of the analyte is considered. Activity-based sensing probes potentiate the study of intricate biological questions previously inaccessible with standard binding- based tools. For instance, chronic inflammation has been linked to a plethora of different dynamic diseased states. In particular, both cancer and neurodegenerative disorders have been associated with an inflammatory microenvironment resulting in progression of these conditions. As such, my thesis work has been focused on the development of activity-based sensing tools to better understand the complex crosstalk between inflammation and disease progression. Chapter 1 is an introduction to molecular imaging with a particular emphasis on activity-based tool development, along with an introduction on inflammatory pathologies, specifically cancer and Alzheimer’s disease. Then, Chapter 2 is an account of the generation of a dual-activated logic-gated probe to explore the role of inflammation (via nitric-oxide) on the cancer stem cell population. Chapter 3 signifies our work in the design and synthesis of a dual-modality probe to explore how a tumor’s oxygenation status alters the stemness profile. Finally, Chapter 4 details our synthetic efforts to obtain a ratiometric photoacoustic probe for the deep tissue imaging of calcium as it relates to disease progression in Alzheimer’s disease.

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

2024

Author dc:creator

• Swartchick, Chelsea Brianna

Contributors dc:contributor

• Chan, Jefferson K
• Mirica, Liviu M
• Sarlah, David
• Silverman, Scott K

• Bioluminescence
• Cancer Stem Cells
• Aldehyde Dehydrogenases
• Fluorescence
• Hypoxia

Statement dc:rights

• Copyright 2024 Chelsea Swartchick

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/125758

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F125758