Harnessing Cyanine Reactivity for Imaging and Drug Delivery

Seminar series
Organic Colloquium
Thu, Nov 1 4:00pm
Franz Hall 1178
Speaker Prof. Martin Schnermann
National Cancer Institute
Department of Chemistry

Abstract: Light provides a uniquely powerful stimulus to visualize and/or perturb biological systems. The use of tissue penetrant near-IR wavelengths enables in vivoapplications, however developing molecules that function in this range remains a substantial challenge. Enabled by modern organic synthesis, we study and then use the chemistry of cyanine fluorophores to develop new long-wavelength optical tools for imaging and drug delivery. In the context of imaging, we prepare novel cyanines with improved properties for in vivo optical imaging and microscopy. Our efforts center on the development of new synthetic methods to enable the preparation of molecules with excellent stability and optical properties. In the context of drug delivery, we have developed a single photon uncaging reaction initiated by light in the 690 to 780 nm range using readily synthesized C4'-dialkylamine-substituted heptamethine cyanines. Small molecule release occurs through a reaction sequence comprising regioselective photooxidative C-C cleavage and then hydrolysis of the C4'-amine. The ability to release therapeutic molecules using the targeted application of near-IR light will facilitate the creation of novel drug delivery strategies. We have developed an antibody-based approach that releases derivatives of the potent anti-cancer agent duocarmycin.  Studies in animal models illustrate that the constructs can be imaged in vivo prior to uncaging, are well tolerated, and display promising efficacy. Details regarding the development of this approach and our long-term goals are described.