Cobalamin as a light-sensitive agent in targeted therapies for a range of diseases

For decades, scientists have invested countless hours developing targeted therapies in search of the elusive “magic bullet” of drug delivery. Many drug delivery vehicles have been tested, from nanoparticles to liposomes to cell-based carriers. Among those tested, red blood cells have emerged as a preferred carrier due to their biocompatibility, large size, and long circulation time. In combination with these vehicles, several triggers, both internal and external, for drug release have been developed. Light is one of the most commonly used release mechanisms, favored for its exquisite spatiotemporal selectivity. Due to the constraints of the therapeutic window of tissue, however, light-based therapies must be developed that respond to 600-900 nm light in order to penetrate tissue sufficiently for therapeutic application.Cobalamin (Cbl, vitamin B12) contains a light-sensitive Co-C bond and is wavelength-tunable via attachment of fluorophores of various wavelength. Herein, I describe recent advancements in Cbl-based drug delivery conducted by the Lawrence lab, including studies of membrane anchoring stability, photolytic efficiency of different alkyl groups, and in vivo tests of thrombolytic protein delivery.