Researchers at the University’s Institute for Regeneration and Repair have developed a sensor that lights up when a drug is released in the body. This technology can be used to improve the design of advanced therapeutic drugs in the future. Dr Ferran Nadal-Bufi, Professor Marc Vendrell and colleagues based in the IRR Chemistry Hub, in collaboration with an industry partner, have developed a special molecule or ‘sensor’ for antibody-drug conjugates (ADCs). This sensor lights up in two conditions - pH changes and when the molecule breaks apart. This allows the researchers to track the movement of ADCs inside cells (when pH lowers) and observe when and where the drug is released (when the drug breaks away from the antibody) in real time under a microscope. Antibody-drug conjugates (ADCs) are a promising type of treatment that deliver drugs directly to target cells, but controlling when and where the drug is released inside the cell is difficult. This is because the processes that guide ADCs into and throughout the cell, and ultimately release their drug are complex. Several methods have been used in the past to track the movement and drug release of ADCs. However, these past methods don’t provide detailed information at the cellular level, or provide information on how they move over time. The new probes overcome this issue. The research team’s results showed that the ADCs need to stay in specific cell compartments, called lysosomes, for 8 hours before the drug is released. Importantly, the small size of these probes did not affect the ADCs' ability to target the right cells, or release the drug effectively. This breakthrough technology offers unprecedented insights into the mechanism of action of ADCs, and it has the potential to transform ADC design from a trial-and-error approach into a more rational strategy, paving the way for next-generation ADCs with improved efficacy and fewer side effects. Ferran Nadal-Bufí IRR Postdoctoral Research Fellow This image shows that the antibody-drug conjugate has recognised, bound to and entered the cells of interest (cyan) and released its drug (yellow) in acidic environments (lysosomes in red). This project was funded by the European Research Council.Read the full paper in the Journal of the American Chemical SocietyVendrell research group Tags CIR Publication date 23 May, 2025
