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.
