Label-free optical signatures of extracellular vesicles and their applications in disease diagnosis and therapy response
Park, Jaena
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https://hdl.handle.net/2142/129571
Description
Title
Label-free optical signatures of extracellular vesicles and their applications in disease diagnosis and therapy response
Author(s)
Park, Jaena
Issue Date
2025-04-25
Director of Research (if dissertation) or Advisor (if thesis)
Boppart, Stephen A.
Doctoral Committee Chair(s)
Boppart, Stephen A.
Committee Member(s)
Cunningham, Brian T.
Dobrucki, Wawrzyniec
Selting, Kimberly A.
Department of Study
Bioengineering
Discipline
Bioengineering
Degree Granting Institution
University of Illinois Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Extracellular Vesicles
Label-Free Imaging
Multiphoton Microscopy
Optical Redox Ratio
Cancer Diagnosis
Therapy Response Monitoring
Urinary Biomarkers
Metabolic Profiling
Tumor Microenvironment
Abstract
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.
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