In a development that could change how medications are delivered in the body, researchers at the University of Geneva have created a system that uses light to activate drugs exactly where and when they’re needed. The advance, published in Nature Communications, could lead to more effective treatments with fewer side effects.
The team developed a method to modify drug molecules so they remain inactive until exposed to a specific light pulse, then become trapped within the targeted cells. This precision targeting could dramatically reduce the systemic effects that make many current medications cause unwanted side effects throughout the body.
A New Approach to Drug Delivery
“Everything started from this methodological question,” explains Monica Gotta, Professor in the Department of Cell Physiology and Metabolism at UNIGE Faculty of Medicine. The team initially sought to control a protein called Plk1, which is involved in cell division, to better understand its role in organism development.
The Chemical Lock and Key
The researchers modified a molecule that inhibits Plk1 by adding two light-sensitive components. One component prevents the drug from working until activated by light, while the other acts as a molecular anchor, keeping the activated drug confined to specific cells.
“After a complex process, we were able to block the active site of our inhibitor with a coumarin derivative, a compound naturally present in certain plants. This coumarin could then be removed with a simple light pulse,” says Victoria von Glasenapp, the study’s first author.
Precision Through Light
The system’s effectiveness was demonstrated in both individual cells and three-dimensional cell cultures. When researchers applied a brief pulse of light to a specific area, only the cells in that region were affected by the drug, while neighboring cells remained unchanged.
This level of control could be particularly valuable for treatments that currently cause severe side effects. In Switzerland alone, thousands of people suffer from serious drug-related side effects annually.
Future Applications
“We hope that our tool will be widely used, leading to a better understanding of how living organisms function and, in the long term, to the development of location-specific treatments,” says Gotta.
The technique could potentially be adapted to many different types of drugs. Future applications might include using simple lasers to activate treatments exactly where needed while sparing surrounding healthy tissue, potentially transforming treatments for conditions like skin cancer and other localized diseases.
A Collaborative Achievement
The research represents a successful collaboration between biologists and chemists. Nicolas Winssinger, Professor in the Department of Organic Chemistry at UNIGE, explains that the team was able to “activate and anchor the inhibitor with the same light pulse,” creating a dual mechanism for precise control of the drug’s activity.
While the system currently works with visible light that can penetrate only a short distance into tissue, the researchers suggest that future developments could potentially use different wavelengths or two-photon activation for deeper tissue penetration, expanding the potential applications of this approach.