Author ORCID Identifier
Date of Award
Doctor of Philosophy (PhD)
Kathryn B Grant
Immune-cell-associated tumor targeting, fluorescence imaging, biodistribution studies, and pH sensing, are vital research in the field of theragnostic. Near-infrared (NIR) cyanine dyes show immense potential in these areas. This thesis presents the development of new diverse scaffolds that address the limitations of traditional small molecules already developed for targeting and imaging. Through a rational approach and molecular engineering, we systematically modified the cyanine skeleton through a facile design and synthetic routes for optimal bioimaging with improved capabilities for targeted tumor delivery, biodistribution studies, and pH sensing. Since the safety of cyanine scaffold is well well-known, rationally designed cyanine fluorophores established in the current study will expand an inventory of contrast agents for NIR imaging of not only normal tissues but also cancerous regions originating from these organs/tissues. By utilizing our developed scaffold, we have tested and proven the concept of structure-inherent tumor targeting (SITT) which eliminates the need for additional chemical conjugation. The emerging SITT mechanism proposes that immune cells originating from the bone marrow or present in the tumor microenvironment could serve as primary targets for cancer detection, owing to their abundance within tumoral tissues. In addition, the superior fluorescence imaging of these new cyanine-based scaffolds were achieved through precise control of optical properties, high quantum yields, and improved photostability. These features result in enhanced sensitivity and resolution, enabling the detection of cellular and tissue targets with higher precision. A comparative pH studies of three unique scaffolds with distinct molecular features reveals that developed scaffolds possess distinctive inherent pH-sensitive properties, enabling real-time pH sensing within biological environments. Integration of pH-responsive fluorophores or pH-indicator dyes allows for accurate monitoring of pH fluctuations in microenvironments. This functionality affords valuable insights
into physiological and pathological processes, aiding in the understanding of pH-related diseases and the development of targeted therapeutic strategies.
Shamim, Md, "Rational Design and Synthesis of NIR Dyes for Biomedical Imaging." Dissertation, Georgia State University, 2023.
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