Researchers activate drugs using infrared light

Spanish scientists have successfully activated molecules located inside cell tissues using two-photon excitation from infrared light lasers, with an efficiency of almost 100%.

It is hoped that photoswitchable molecules — compounds that, in the presence of certain light waves, change their properties — can be used in future to have absolute control of the activity of a molecule in an organism, including deciding when, where and how a drug is activated. Thanks to the results of a study led by the Institute for Bioengineering of Catalonia (IBEC) together with the Universitat Autònoma de Barcelona (UAB), the scientific community is one step closer to achieving this objective.

The photoswitchable molecule that the researchers have used is a new variant of azobenzene, a chemical compound that has a flat shape in the dark but bends when exposed to light. Photopharmacology seeks to take advantage of this peculiar property to control the activity of drugs.

The idea is that an inactive drug combined with azobenzene is introduced into the body. The design of the drug only allows its operation when the azobenzene is bent. In this way, despite having a drug distributed throughout the body, it will only take effect at the points where the light that stimulates azobenzene is irradiated, thus avoiding the side effects associated with the drug’s action in areas where azobenzene is present.

Until recently, techniques based on photoswitchable molecules used continuous-wave lasers of violet or blue light (one-photon stimulation) to activate these compounds — a method that does not allow for focalising the stimulus. As noted by UAB researchers Jordi Hernando and Ramon Alibés, “We wanted the molecule to be activated at a specific point, not along the whole beam of light that we irradiate.

“We saw that two-photon transitions using pulsed infrared light allowed to achieve this, but the efficiency was very low, and the applications were limited. The molecules we have developed now achieve this effect with 100% efficiency. It is a very robust and precise technology to manipulate neuronal activity.”

The researchers have now proven the effectiveness of their technique on mouse neurons and in an animal model for the study of neuronal circuits, the Caenorhabditis elegans worm. Despite the cells in a neuronal tissue being very close together, the researchers managed to select those in which they wanted to activate the photoswitchable molecule.

The results of this development, published in the journal Nature Communications, have great potential since they open the door to new lines of research in the molecular field. With the technique described, scientists will possess unprecedented spatiotemporal control over any photoswitchable molecule they wish to investigate.

“It’s a development that opens the door to a large number of applications,” said Pau Gorostiza, head of the Nanoprobes and Nanoswitches Group at IBEC. “From drugs that only act at the point of our body that is illuminated and are therefore free from unwanted side effects in other regions, to the spatial and temporal control of any protein whose function we want to study in the context of an organism.”

Image caption: Control of the activity of individual worm neurons through two-photon stimulation. In the image, a neuron in the tail of the worm (enlarged square region) is stimulated with pulses of infrared light in the presence of the new molecule and an activation response occurs. Image credit: Montserrat Porta, Aida Garrido.

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