Strategic tuning of near-infrared dyes to access novel biomedical applications

Brady, Catharine J.

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https://hdl.handle.net/2142/124282 Copy

Description

Title

Strategic tuning of near-infrared dyes to access novel biomedical applications

Author(s)

Brady, Catharine J.

Issue Date

2024-04-18

Director of Research (if dissertation) or Advisor (if thesis)

Chan, Jefferson

Doctoral Committee Chair(s)

Chan, Jefferson

Committee Member(s)

• Mirica, Liviu
• Murphy, Catherine
• Sweedler, Jonathan

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• photodynamic therapy
• hemicyanine dye
• photoacoustic imaging

Abstract

Light is a powerful tool for the development of novel biomedical applications such as photoactivable therapeutics and optical molecular imaging techniques. The use of light as an external activation or excitation method allows for enhanced spatial and temporal control in vivo, as well as the ability to further optimize its applications via adjustment of the wavelength, power output, and time of irradiation. Small molecule organic chromophores can be strategically tuned in their light absorbing and energy decay properties to meet the criteria for different biomedical purposes. In particular, the fluorescent hemicyanine dye (HD) platform is ideal for in vivo applications due to its near-infrared light absorbing properties, proven biocompatibility, intrinsic tumor targeting capabilities, and ease of synthetic modification. Herein, we report the strategic design and rational modification of the HD scaffold to access new applications in cancer treatment with photodynamic therapy and in deep tissue molecular imaging through photoacoustic imaging. Traditional cancer chemotherapeutics interfere with important biological processes, therefore resulting in severe side effects to healthy tissue because they lack selectivity for cancer cells. Further, cancer can develop resistance to drugs, rendering them ineffective. Chapter 2 discusses the development of a HD photosensitizer, PS-HD, for photodynamic therapy, a unique therapeutic modality in which toxic levels of reactive oxygen species can be generated upon light excitation. Light can be selectively dosed to cancer cells leading to increased oxidative stress and eventually cellular death to overcome the challenges of common drugs. A glutathione responsive version of PS-HD was developed to further enhance the cancer targeting properties. Molecular imaging is powerful non-invasive technique that allows for the real-time visualization of molecular events in a complex in vivo environment. This enables a more comprehensive of understanding of the processes unfolding at the biological level and has important applications in discovering new biology, early detection of disease, personalized medicine, and assessing therapeutic candidates in the drug discovery and development pipeline. Chapter 3 reports on the development of an optimized HD, photoacoustic-HD, for photoacoustic imaging, a molecular imaging technique that marries the advantages of fluorescence imaging and ultrasonography for enhanced deep tissue imaging. Three activity-based sensing probes were generated using photoacoustic-HD and applied for in vivo molecular imaging to demonstrate the utility of the scaffold.

Graduation Semester

2024-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2024 Catharine Brady

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