Light-responsive agents offer the promise of targeted therapy, whose benefits include (i) prolonged action at the target site, (ii) overall reduced systemic dosage, (iii) reduced adverse effects, (iv) and localized delivery of multiple agents. Although photo-activated pro-drugs have been reported, these species generally require short wavelengths (&lt;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 most existing photo-cleavable functional groups. Furthermore, since multi-drug therapy holds promise for the treatment of complex diseases, from cancer to neurological disorders, controlling the action of multiple drugs via wavelength modulation would take advantage of a property that is unique to light.<br/>            We have developed a vitamin B12/light-facilitated strategy for controlling drug action using red, far red, and NIR light. The technology is based on a light-triggered reaction displayed by a subset of B12 derivatives: alkyl-cob(III)alamins, which suffer photo-homolysis of the C-Co(III) bond. The C-Co(III) bond is weak (&lt;30 kcal/mol) and therefore all wavelengths absorbed by the corrin ring (330 – 580 nm) induce photo-cleavage. In addition, by appending fluorophores to the corrin ring, long wavelength light (&gt;600 nm) is readily captured and used to separate the Co-appended ligand (e.g. a drug) from B12. Consequently, it is now feasible to pre-assign the wavelength of homolysis by simply installing a fluorescent antenna with the desired photophysical properties. The wavelength malleability inherent within this strategy has been used to construct photo-responsive compounds that launch different drugs by simply modulating the wavelength of illumination. In addition, these phototherapeutics have been installed on the surface and interior of cells, such as erythrocytes or neural stem cells, and released upon exposure to the appropriate wavelength. <br/>

Illuminating the path for drug delivery

254th National Meeting (2017)

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