Label-free optical signatures of extracellular vesicles and their applications in disease diagnosis and therapy response

Extracellular vesicles (EVs) have emerged as critical mediators of cell-to-cell communication, particularly in the tumor microenvironment, where they modulate hypoxia response, drug resistance, and metastatic progression. Beyond these roles, EVs are promising candidates for noninvasive cancer diagnostics and therapy monitoring through liquid biopsy. However, a fundamental barrier to clinical translation lies in the difficulty of characterizing EVs in situ while preserving their biochemical composition, spatial origin, and functional state. Traditional EV analyses often rely on bulk or destructive molecular profiling, limiting their diagnostic specificity and obscuring biologically relevant heterogeneity. More critically, it remains unclear whether the metabolic content of EVs reflects the state of their parental cells. To address these challenges, this thesis integrates label-free intravital and ex vivo optical imaging to investigate the metabolic characteristics of EVs across multiple oncologic conditions, including hypoxia, chemotherapy, and radiotherapy. Simultaneous label-free autofluorescence-multiharmonic (SLAM) microscopy enables high-resolution imaging and real-time metabolic profiling of EVs using endogenous optical contrast from coenzymes found in EVs. Across tumor models and biofluid-derived EV populations, optical redox ratio (ORR) imaging was used to assess metabolic reprogramming associated with disease state and treatment response. The findings demonstrate that autofluorescence-based EV profiling supports noninvasive, functionally informative liquid biopsy for cancer screening, prognostication, and therapy assessment by capturing dynamic metabolic shifts reflective of parent cell states.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Bioengineering

Grantor

University of Illinois Urbana-Champaign

Year dc:date

2025

Author dc:creator

• Park, Jaena

Contributors dc:contributor

• Boppart, Stephen A
• Boppart, Stephen A.
• Cunningham, Brian T.
• Dobrucki, Wawrzyniec
• Selting, Kimberly A.

• Extracellular Vesicles
• Label-Free Imaging
• Multiphoton Microscopy
• Optical Redox Ratio
• Cancer Diagnosis
• Therapy Response Monitoring
• Urinary Biomarkers
• Metabolic Profiling
• Tumor Microenvironment

Statement dc:rights

• Copyright 2025 Jaena Park

Language dc:language

en, eng

Handle dc:identifier

https://hdl.handle.net/2142/129571

OAI record oai:identifier

https://www.ideals.illinois.edu/oai-pmh?verb=GetRecord&metadataPrefix=etdms&identifier=oai%3Awww.ideals.illinois.edu%3A2142%2F129571