PHILADELPHIA – Using Förster resonance energy transfer (FRET) to chart the disintegration of nanoparticles in living tissue could aid the development of safe nanodrug-delivery methods. “Nanoparticles are made with very diverse designs and properties, but all of them need to be eventually eliminated from the body after they complete their task,” said Dr. Michael Chorny, a cardiology researcher with the Children’s Hospital of Philadelphia (CHOP). This is “a necessary step in translating nanoparticles into clinical use,” he noted. He and his colleagues used FRET as a molecular ruler to measure the distance between the components of nanoparticles in liquid and semiliquid media, as well as in vascular cells. By labeling the formulations with fluorescent probes, the study demonstrated the radiation-free transfer of energy within the same particle. As the particles disassembled, the fluorescence gradually disappeared. The researchers monitored the change without separating the particles from their environment, which allowed undistorted and continuous measurements of their integrity. Nanoparticle disassembly causes a shift in the fluorescence pattern. Courtesy of Children’s Hospital of Philadelphia. The use of biodegradable nanoparticles for medical applications has been studied extensively over the years. In some cases, external magnetic fields were used to guide iron oxide-impregnated nano-particles to metallic arterial stents. But continuously monitoring nanoparticles in model biological settings and living cells without disrupting cell function remained difficult. “Accurately measuring nanoparticle disassembly in real time directly in media of interest, such as the interior of a living cell or other types of complex biological milieus, is challenging,” Chorny said. “Our goal here was to develop such a noninvasive method providing unbiased results. These results will help researchers to customize nanoparticle formulations for specific therapeutic and diagnostic applications.” Disintegration is likely to occur more rapidly early in the vessel healing process and to slow down later, Chorny said. “This may have implications for the design of nanoparticles intended for targeted drug, gene or cell therapy of vascular disease. Nanoparticles could be formulated with contrast agents for diagnostic imaging, or could deliver anticancer drugs to a tumor.” The research was published in Proceedings of the National Academy of Sciences (doi: 10.1073/pnas.1324104111).