Efficient red-to-NIR photo-uncaging and applications in therapy

PROJECT SUMMARY Many light-responsive systems have been produced via natural evolution, including opsins, and phytochromes, while chemists have added to the list of light-responsive molecules for new tools. Scientists have embraced the use of these light-responsive tools to construct new materials, and we’ve just scratched the surface of the potential in this important field, particularly in the direction of making efficient red-to-near-infrared (red-to-NIR) light-responsive groups. The promise of red-to-NIR light resides in deeper penetration depth, less scattering and absorption by the sample, and less photodamage. Though approaches that use two-photon and lanthanide nanoparticles exhibit promising progress in allowing red-to-NIR absorption, developing organic-based materials that work under low power LED light is still challenging and such materials would expand the toolboxes and facilitate addressing a number of urgent questions. The organic-based platforms will benefit the fundamental understanding of chemical structure-to-property relationships, as well as impact many intriguing emerging applications, such as precision drug delivery, neuron modulation, light-triggered reactions, and gene therapy activation. Because of the much lower photon energy in the red-to-NIR region compared with UV and blue light, efficient red-to-NIR responsive is still challenging. This proposal aims to develop novel boron-dipyrromethene (BODIPY) based photo-uncaging groups that build upon weak covalent N-O bond. In particular, the weak dissociation energy of N-O permits the cleavage after absorbing low energy red-to-NIR photon, which is ideal for biological and biomedical applications. By varying and modifying the chemical structures, we intend to increase photo-uncaging efficiency by rigidifying the structure and for the first time facilitate dual cargo release from BODIPY. After conjugating with a cancer targeting unit, biomedical applications of these novel photo-uncaging materials will be demonstrated in vitro and in vivo in light-triggered drug delivery. Overall, the capability of efficient photo-uncaging in the red-to-NIR window will support more advanced experimental designs, and the convergence of basic research with applications will contribute to expanding knowledge while benefiting undergraduate researchers for broad impact.