A new avenue for targeted drug delivery has been proposed by researchers from The Grainger College of Engineering at the University of Illinois Urbana-Champaign. Their findings, published in Materials Today Bio, report the first successful application of metabolic labeling in platelets.
Platelets are anucleate cell fragments that congregate at sites of bleeding and inflammation to clot blood. Their unique properties make them attractive vehicles for targeted drug delivery systems. However, platelets are notoriously difficult to engineer due to their small size and physiologic simplicity.
“Cells can usually be engineered with a genetic or chemical approach,” said the senior author of the paper, Assistant Professor Hua Wang of the Department of Materials Science and Engineering. "But platelets don’t have a nucleus or the typical DNA machinery, which makes them difficult to genetically engineer.”
Instead, researchers turned to a chemical approach, which relies on chemical tags — molecules used to track the activity of other biomolecules such as proteins, lipids, or sugar compounds. Scientists can mix an incubated cell with a sugar compound, wait for the sugar to metabolize, and observe a tag expressed on the cell membrane. This process is known as metabolic glycan labeling and has shown promise in targeted drug delivery systems.
Wang’s lab had previously demonstrated successful metabolic labeling in cancer and immune cells. Until now, this labeling was limited to cell types with the kind of DNA machinery that allows rapid cell division. But Wang and his colleagues wondered: Could they tag something without a nucleus? This query inspired their focus on platelets.
Working in stages, the researchers began by testing their method in vitro, or inside a cell culture medium. After isolating mouse platelets and culturing them with a sugar compound, the group observed chemical tags on the surface of platelets in just a few hours. Their results were validated using a combination of flow cytometry, fluorescent microscopy, and western blotting techniques.
Next they shifted to an in vivo model, wanting to explore the process in an actual biological system. Injecting mice directly with the sugar compound produced the same outcome, and the combination of in vivo and in vitro approaches allowed researchers to visualize and quantify these chemically tagged cell membranes.
Scientists are optimistic that specially tagged platelets can be used as drug-delivery vehicles for cancer, immune diseases, and blood clotting disorders. And because platelets have a short half-life, the cargo attached to them become cleared within days, alleviating concerns over drugs remaining in the body long-term.
Going forward, the Illinois Grainger Engineering researchers will collaborate with outside laboratories to continue work on the drug-delivery side, providing guidance on chemically modifying platelets to accept more cargo and in a more stable manner.
“We have good confidence in how much cargo we can load and how stable they are,” Wang said. “In terms of our lab, we are very interested in the metabolic labeling technology. We want to further improve both in vitro and in vivo labeling efficiency, which we think could be useful to many researchers in the field.”
Illinois Grainger Engineering Affiliations
Hua Wang is an Illinois Grainger Engineering assistant professor of materials science and engineering and is affiliated with the Cancer Center at Illinois, the Department of Bioengineering, the Materials Research Laboratory, the Beckman Institute for Advanced Science and Technology, the Carle Illinois College of Medicine and the Carl R. Woese Institute for Genomic Biology. He can be reached at huawang3@illinois.edu.