Isha Nadig Rose Hills
A General Approach to Immunotargeting Near-Infrared Fluorophores
Bioimaging is crucial for fundamental studies of cell function, diagnosing diseases, monitoring treatment responses, and guiding surgical studies. However, bioimaging through tissue is challenging due to substantial scattering and autofluorescence in tissue at visible wavelengths (400-700 nm). To address this challenge, we will synthesize red-shifted polymethine fluorophores derived from cyanine or flavylium scaffolds, with emission wavelengths from 780 to 1100 nm. To confer the fluorophores with immunotargeting capabilities, we conjugate them to immunoglobulin G (IgG) antibodies to selectively bind to receptors on breast and ovarian cancer cells. The B1 domain of Streptococcal protein G (GB1), mutated to express two Cys residues, enables stable conjugation of two fluorophores through maleimide chemistry. By leveraging the high affinity of GB1 to the Fc region of IgG, fluorophore-GB1 constructs are readily assembled with IgG to form fluorescent immunoconjugates for live cell and animal imaging. The modularity of this system allows for precise conjugation to a variety of probes, highlighting its potential applications for clinical diagnostics and optically-guided surgery.
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