Light-activated prodrugs enable rapid, spatially discrete activation of therapeutic molecules. However, their widespread implementation has been impeded by a number of technical challenges, including toxicity, poor tissue penetrance of short wavelength light, and a deficit of suitable drug delivery vehicles. In this work, we demonstrate a possible solution to many of these challenges, via a cobalamin (vitamin B12)-based methodology that utilizes long wavelength light to trigger the release of therapeutic compounds internalized within erythrocytes. In this study, we initially characterize the quantity of photoproducts released from erythrocyte carriers upon exposure to 520 nm light and subsequently demonstrate the biological impacts of the photo-released anti-inflammatory compounds Methotrexate, Taxol, and Colchicine via CETSA (Cellular Thermal Shift Assay) and microtubule polymerization assays. We then employ a series of fluorophore-linked cobalamin prodrugs to release these anti-inflammatory compounds from within erythrocytes with long wavelength light (650 – 800 nm). Finally, we utilize wavelength-assigned orthogonal release experiments to demonstrate independent release of phototherapeutics from a single pool of erythrocyte carriers.

Long wavelength, orthogonal release of internalized anti-inflammatory compounds from cellular vehicles

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.