Light Activated Drugs

Light has been used, in conjunction with light-responsive agents, to control the biochemistry of cells, manipulate the behavior of organisms, and treat diseases such as cancer. We have designed a host of light-responsive sensors, inhibitors, activators, and proteins that provide the means to assess or influence intracellular enzymology with exquisite temporal and spatial control.

In addition, we have recently developed a vitamin B12/light-facilitated strategy for drug delivery using far red and near IR light. Light-responsive agents offer the promise of targeted therapy, whose benefits include

• (i) prolonged action at the diseased site
• (ii) reduced dosage since therapeutic efficiency is enhanced
• (iii) reduced adverse effects and reduced toxicity as a result of selective enhancement
• (iv) localized delivery of multiple agents resulting in targeted combination therapy.

Although photo-activated pro-drugs have been previously reported, these species require short wavelengths, less than 450 nm, for activation. Unfortunately, short wavelength light does not penetrate the skin. By contrast, maximal tissue penetrance of light occurs within the "optical window of tissue," 600 – 900 nm, well beyond the wavelength range of existing photo-cleavable functional groups. Members in our group have developed a light-mediated strategy that controls the release of drugs in a wavelength-assigned fashion, including within the optical window of tissue. We are currently exploring the application of these agents for the treatment of rheumatoid arthritis and cancer, as well as remodeling the vasculature.