Controlling processes in living organisms with light could be useful in research and medicine. One approach for this is optogenetics, where light is used to control genetically modified cells—in a heart, for example. However, this approach is difficult to use clinically due to the challenges of genetic modifications.
Pau Gorostiza, Barcelona Institute for Science and Technology (BIST), Spain, Network Biomedical Research Center in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), Madrid, Spain, and Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain, and colleagues have developed a method to control heart function without genetic changes. The team used a photoswitchable drug named Phthalimide-Azo-Iperoxo (PAI), which contains a central diazo group. This group can be switched between its cis- and trans-forms using light.
The drug targets muscarinic acetylcholine receptors (mAChRs), which regulate the heart rate. The trans-form of PAI reduces the heart rate. This effect can be stopped by converting it to the cis-form using UV light. The process can be reversed by using blue light to convert PAI back to its trans-form. The team tested the effects in translucent tadpoles and found that they could control the animal’s heart rate. The drug could also be switched with near-infrared (NIR) light, which would allow its use in non-translucent tissues.
- Optical Control of Cardiac Function with a Photoswitchable Muscarinic Agonist,
Fabio Riefolo, Carlo Matera, Aida Garrido-Charles, Alexandre M. J. Gomila, Rosalba Sortino, Luca Agnetta, Enrique Claro, Roser Masgrau, Ulrike Holzgrabe, Montserrat Batlle, Michael Decker, Eduard Guasch, Pau Gorostiza,
J. Am. Chem. Soc. 2019.