Photo-Uncaging and Delivery of Bioactive Small Molecules

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In this project funded by the Chemical Structure, Dynamics & Mechanisms B Program of the Chemistry Division, Professor Peter C. Ford of the Department of Chemistry and Biochemistry at the University of California, Santa Barbara is developing systems that can release bioactive small molecules when signaled by light. Small molecules such as nitric oxide (NO) and carbon monoxide (CO) play important roles in regulating functions such as blood pressure and inflammation. The ability to control the release of these small molecules in the body may also have therapeutic values in cancer treatment and wound healing. In this research, very small, metal containing particles are designed to bring NO, CO and other small molecules to specific sites in the body. Once at the site, the particles are exposed to light and release their "cargo". This targeted delivery of small molecules may eventually reduce the side effects of chemotherapy by lowering the dosage amount of certain drugs. The project involves aspects of synthetic inorganic and nanomaterial chemistry, mechanistic photochemistry and photophysics, as well as chemical biology. The graduate and undergraduate student researchers involved have the opportunity to make fundamental contributions to these fields and to broaden their scientific experience to be better positioned for contributing to a changing technical world. The researchers are also active in various outreach activities, including regular visitations to science classes at regional high schools to put a human face on the word "scientist" for an economically and ethnically diverse group of high school students. This project has three themes: (1) designing metal complexes conjugated to antennas that utilize deep tissue penetrating near-infrared (NIR) light as the excitation source; (2) developing carriers for these conjugates that target desired sites; and (3) mechanistic studies of the reactions of carbon disulfide (CS2) with various nucleophiles under biologically-relevant conditions and the design and photoreactions of potential CS2 precursors. The antennas include semi-conductor quantum dots and lanthanide doped upconverting nanoparticles that can be activated by multi-photon excitation at near infrared (NIR) wavelengths. Polymer-based nano- and micron-sized devices are as carriers with the above conjugates. Biological mechanisms such as targeting proteins and immune cells are recruited to deliver these conjugates to sites where NIR excitation leads to targeted release. The third theme is motivated by the possibilities that CS2 is an unrecognized regulator and/or that directed release has potential therapeutic value.