Development of chemical tools for biomarker detection and targeted therapeutics for precision medicine

Activity-based and activatable approaches can facilitate the development of precision medicine to design better drugs and more effective treatment strategies. Activity-based sensing enables the advancement of basic science through real-time biomarker tracking in live animal models. On the clinical end, activity-based sensing improves current diagnostics for more sensitive and earlier detection of potentially life-threatening diseases, such as cancer. Through the development of activity-based and activatable chemical tools, drugs can be repurposed or redesigned to enhance efficacy and attenuate side effects. My thesis work highlights the power of reaction-based technology in the drug-development pipeline with projects to highlight each of these key clinically relevant applications. Treatment strategies can be precisely tuned to maximize efficacy by taking advantage of unique differences in disease microenvironments that exist between individuals. In Chapter 1, the core principles of molecular imaging and drug design are introduced. Chapter 2 reports on the development of a small-molecule tool that enabled the investigation of nitric oxide to establish a link between diets and cancer progression, emphasizing the importance considering lifestyle choices when a patient is diagnosed with cancer. Chapter 3 discusses the development of a multivalent targeting ligand by taking advantage of sugar transporters upregulated in cancer. The multivalent ligand was synthesized in a modular fashion to maximize generalizability. Chapter 4 highlights the development of a photo-degradable nanogel delivery system to repurpose FDA approved drugs and improve their pharmacologic properties. Finally, Chapter 5 discusses the application and protocol optimization of a small-molecule probe for both basic science research and clinical use. Each chapter describes the design rationale, characterization, and appropriate models to showcase the utility of activity-based or activatable methods.

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

2023

Author dc:creator

• Lee, Michael Chi

Contributors dc:contributor

• Chan, Jefferson
• van der Donk, Wilfred A.
• Olshansky, Lisa
• Mehta, Angad

• Chemical Biology
• Precision Medicine
• Biomarker
• Therapeutics
• Probes
• Activity-based Sensing
• Biomedical Imaging
• Molecular Imaging

Statement dc:rights

• Copyright 2023 Michael Lee

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/122219

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F122219