2026-09-24T07:43:14Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/125758 2026-02-03 col_2142_5131 col_2142_14789 com_2142_5130 com_2142_14788 com_2142_8903

application/pdf en text Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2026-08-01 The student, Chelsea Swartchick, accepted the attached license on 2024-06-20 at 12:04. The student, Chelsea Swartchick, submitted this Dissertation for approval on 2024-06-20 at 12:20. This Dissertation was approved for publication on 2024-06-27 at 15:50. DSpace SAF Submission Ingestion Package generated from Vireo submission #20856 on 2025-02-04 at 21:25:02 Rational design of activity-based sensing probes to reveal the impact of inflammation on human disease progression Swartchick, Chelsea Brianna 2024-06-27 Chan, Jefferson K Chan, Jefferson K Mirica, Liviu M Sarlah, David Silverman, Scott K Bioluminescence Cancer Stem Cells Aldehyde Dehydrogenases Fluorescence Hypoxia eng 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. 2024-08 Thesis https://hdl.handle.net/2142/125758 Copyright 2024 Chelsea Swartchick Chemistry Chemistry University of Illinois at Urbana-Champaign Ph.D. Dissertation