Scientists at the University of Geneva (UNIGE) have developed a tool that uses light to precisely control when and where drugs start to work, ensuring they work exactly where they are needed. For drug treatments to be effective and minimize side effects, they must work at the right time and place -- something that remains an elusive challenge.
Now, a team of biologists and chemists at the United Nations University has created a system that activates molecules with brief light pulses of just a few seconds. By testing one protein that is essential for cell division, the method could be applied to other molecules, with promising applications in both research and medicine. It could even improve existing treatments, such as those for skin cancer. The findings were recently published in Nature Communications.
After the drug enters the human body, it not only affects the target organ, but also spreads throughout the body, affecting the entire body. This lack of precision can lead to two major risks: the drug may not reach its target site effectively, reducing its intended efficacy, or it may cause serious side effects. In Switzerland alone, thousands of people suffer serious side effects related to medications every year.
The idea is simple: activate the drug precisely at a predetermined location. However, turning this idea into reality is complex. If successful, this approach could allow scientists to activate or deactivate proteins in specific regions of the body, allowing them to better understand their function and improve targeted treatments.
"It all started with this methodological problem," recalls Monika Gota, professor in the Department of Cell Physiology and Metabolism at the UNU School of Education's Faculty of Medicine, who co-initiated and coordinated the study with Nikolai Winsinger, professor in the Department of Organic Chemistry in the UNU School of Education's Faculty of Science. "We were looking for a way to inhibit Plk1, a protein involved in cell division, when and where we wanted to better understand its function during the development of the organism."
"By combining expertise in chemistry and biology, the scientists engineered the Plk1 inhibitor molecule so that it could be activated by light pulses. Through a complex process, we blocked the active site of the inhibitor with a coumarin derivative, a compound naturally found in certain plants." said first author Victoria von Glasenapp, a postdoctoral researcher in the laboratories of Professor Gota in the Department of Medicine and Professor Wenzinger in the School of Science.
"The challenge for us remained to find a way to anchor the inhibitor at the exact location in the body where it needs to act," explains Nicholas-Winsinger. "We therefore modified the inhibitor so that it became trapped in the target cell by adding a molecular anchor that is only released under light." This allowed us to activate and anchor the inhibitor with the same light pulse, thereby inactivating Plk1 and halting cell division at the precise desired location. "
The system developed by scientists can use light to control the activity of molecules in organisms in space and time. It can be applied to a variety of molecules, activating the drug only where needed. So, in the future, a simple laser could activate treatment exactly where it's needed, while sparing surrounding healthy tissue and thus limiting unwanted side effects. "We hope that our tools will be widely used, allowing a better understanding of how organisms function and, in the long term, the development of site-specific treatments," concludes Monica Gotta.
Compiled from /ScitechDaily