Using light to control nanoreactors

In nature, biochemical processes often rely on a system being pushed out of equilibrium before automatically returning to its resting state. One such instance is the mechanism by which light receptors operate in the human eye, which has inspired Adolphe Merkle Institute researchers to develop nanoreactors that function using the same principle.

A molecule within the eye’s retinal receptors changes its structure when irradiated with light, and an enzymatic reaction subsequently converts the molecule back into its original form. Without this capacity to re-vert back to their initial state, the receptor cells would not be able to sense light repeatedly.

Researchers from Professor Nico Bruns’ Macromolecular Chemistry group, along with colleagues at the Swiss Federal Laboratories for Materials Science and Technology (Empa) in St. Gallen, adopted this general principle as their blueprint for developing artificial light-responsive catalytic nanoscale systems.

“We were intrigued by a novel class of photoswitches called Donor-Acceptor-Stenhouse-Adducts (DASAs), that colleagues at the University of California, Santa Barbara, have developed,” explains Bruns. “They switch from a less polar resting state to a more polar isomer in presence of visible light, and return back to their resting state when the light is switched off.”

Bruns and his team integrated such DASA molecules into the membrane of polymer nanocapsules. Upon irradiation with light, the DASAs switch, increasing the polarity of the capsule membrane. As a result, the capsules become permeable for water-soluble substances. This effect can be used to trigger the re-lease of cargo from the nanocapsules. More intriguingly, capsules that host enzymes, in other words, biological catalysts, can be switched from an inactive state in the dark to a catalytically active state when irradiated with visible light. This active state lasts as long as light is present. Once returned to darkness, these nanoreactors automatically revert back to their original state with no catalytic activity. DASAs exist in several colors, which allowed the researchers to create nanoreactors that switch on in response to light of a specified color, such as white, red, or green. By encapsulating one type of enzyme in purple nanocapsules and a second type of enzymes in blue nanoreactors, a mixture of catalysts was obtained that can control and orchestrate enzymatic cascade reactions, kick-started by the different colored lights.

“Light switches can be used for the entire spectrum of colored light from blue to red,” notes Empa researcher Luciano Boesel. “This provides scope to control the release of several drugs or complex reaction cascades in a single patch.”

Not every medication can be swallowed or pumped into the body with a syringe. Yet, the skin – our largest organ – offers a large permeable surface that readily absorbs active substances. Nicotine replacement, pain therapy, or contraception drugs are already applied through the skin using patches. Now, the Empa researchers are also considering these nanocapsules for use in light-switchable patches for transdermal drug delivery. This future development would enable, for instance, a non-invasive delivery method of essential drugs for premature babies. By embedding drug-filled, light-switchable nanocontainers into patches, the team aims to create the next generation of light-controlled transdermal drug delivery systems.

Work on the concept of light-switchable nanoreactors is being pursued within the framework of the National Centre of Competence in Research (NCCR) Bio-Inspired Materials. The nanoreactors could be used to produce pharmaceutical products on demand, for example within a cell, or to produce active com-pounds such as drugs during medical treatment in a controlled fashion.

“We have created a platform technology that is very versatile. For instance, we will investigate how to equip polymers with types of DASAs that switch at wavelengths that span the whole visible spectrum, ideally also reaching the near infrared region,” Bruns reveals. “This could be very beneficial, as infrared light penetrates deeper into tissue than visible light. This way, we could create light-responsive drug delivery nanosystems that could be activated by irradiation of tissue through the skin.”

Reference: Rifaie-Graham, O., Ulrich, S., Galensowske, N.F.B., Balog, S., Chami, M., Rentsch, D., Hemmer, J.R., Read de Alaniz, J., Boesel, L.F., Bruns, N. Wavelength-Selective Light-Responsive DASA-Functionalized Pol-ymersome Nanoreactors, J Am. Chem. Soc., 2018, 140, 25, 8027