Design and Application of Photoresponsive Modules in Circulating Erythrocytes

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Project Summary The use of light to activate therapeutic agents at diseased sites offers the advantage of aggressive treatment with exquisite spatial and temporal control, thereby reducing potential deleterious side effects at unintended sites. Although photo-activated pro-drugs have been reported, these species require short wavelengths (<450 nm) for activation. However, maximal tissue penetrance by light occurs within the “optical window of tissue” (600 – 900 nm), well beyond the wavelength range of existing photo-cleavable functional groups. We’ve developed a new technology that transforms drugs into light responsive “phototherapeutics” that are conveyed by circulating erythrocytes. The proposed research program seeks to address several fundamental questions associated with light responsive therapeutics: (1) What is the mechanism of light capture and drug release in the B12-based molecular scaffolds, (2) what is the optimized structural relationship between the light capturing antennas and the photolysis of the B12-drug bond, (3) what is the scope of therapeutic agents that are amenable to this photo-technology, (4) do phototherapeutics furnish an enhanced therapeutic window relative to the standard of care, and (5) what is the relationship between the activation wavelength and the therapeutic window?