Scientists have long been interested in using red blood cells for drug delivery and imaging. but safely modifying them inside the body has remained a major challenge.
Researchers in the Wang Lab at the University of Illinois Urbana-Champaign have developed a new approach that allows them to chemically tag circulating red blood cells and use them to carry imaging agents and therapeutics for much longer periods of time. In their study, In Vivo Metabolic Tagging and Targeting of Circulating Red Blood Cells, Cancer Center at Illinois (CCIL) member Hua Wang and Yusheng Liu, a doctoral student in materials science and engineering, introduce a method for labeling red blood cells in vivo and attaching different types of molecules to their surface.
“This is the first report of successful metabolic glycan labeling of red blood cells,” Wang said. “This was considered unlikely, because red blood cells do not have nuclei and lack the normal protein production machinery.”
The team’s method works by introducing small chemical tags onto the surface of red blood cells. These tags act as anchors that allow other molecules, such as imaging agents or drugs, to attach to the cells while they circulate in the bloodstream. This red blood cell labeling and targeting technology enables prolonged circulation of anticancer drugs in the bloodstream from hours to days or even longer and is widely applicable to different types of anticancer drugs.
One of the most notable findings from the study is how long these tags last. “The chemical tags can persist on the surface of red blood cells for weeks,” Wang said. “The conjugated cargos can also circulate in the blood for over five weeks, which is much longer than most compounds that are typically cleared within hours or days.”
Cancer Center at Illinois member Hua Wang (left) and Yusheng Liu, a doctoral student in materials science and engineering
Because red blood cells have a long lifespan—about 120 days in humans—they are especially useful for applications that need long-term circulation.
“Red blood cells take up more than 99% of blood cells and have a long-life span,” Wang said. “This makes them an attractive target for drug delivery and imaging applications.”
Previous approaches to engineering red blood cells often required removing the cells from the body, modifying them in a lab, and then putting them back into the bloodstream. These methods can be time consuming and may damage the cells.
The researchers also demonstrated several potential applications of this method. By attaching fluorescent molecules, they were able to improve imaging of blood vessels and tumors. They also showed that MRI contrast agents could stay in circulation longer, allowing for extended imaging with fewer doses.
In addition to imaging, the method could be used to improve drug effectiveness by extending their circulation in the bloodstream.
“Drugs are often cleared from the bloodstream quickly,” Liu said. “By attaching them to red blood cells, we can extend how long they circulate and potentially improve their effectiveness.”
The technology is still in early stages. Right now, only a portion of circulating red blood cells can be labeled, and the team is working to improve that.
“We are still trying to further improve the in vivo red blood cell labeling efficiency and find the most compelling applications for this technology,” Liu said.
Looking ahead, the researchers are interested in exploring how this approach could be used in different areas of medicine, including cancer.
“We are trying to identify the best applications to move forward for this technology via collaboration with Prof. Shuming Nie in BioE, Prof. Fan Lam in BioE, Prof. Matthew Berry in Vet Med, and many others,” Wang said.
Hua Wang
Associate Professor, Materials Science & Engineering
Research Program and Theme
- Program: Cancer Engineering and Biological Systems
- Theme: Comparative and Engineered Oncology Models
Research Focus
Hua Wang’s laboratory aims to understand how cells can be manipulated and engineered to facilitate targeted delivery of therapeutics and to regulate intercellular interactions, thereby improving and innovating therapies for cancers, injured tissues, autoimmune disorders, and other diseases. In one path towards this goal, his lab utilizes chemistry, chemical biology, and synthetic biology tools to modify or engineer cells for subsequent tracking and targeted modulation in vivo. Along another path, his lab develops biomaterials that can target and manipulate immune cells in vivo and applies them to the development of cancer vaccines, cell therapies, and medical devices.
Editor’s notes:
Hua Wang is a professor of Materials Science and Engineering and Bioengineering at the University of Illinois Urbana-Champaign. He is also affiliated with the Cancer Center at Illinois, Department of Bioengineering, Department of Chemistry, the Materials Research Laboratory, the Beckman Institute for Advanced Science and Technology, and the Carl R. Woese Institute for Genomic Biology. His research focuses on biomaterials, drug delivery, and cancer nanotechnology.
He can be reached at huawang3@illinois.edu.
To contact Yusheng Liu, he can be reached here.
The paper “In Vivo Metabolic Tagging and Targeting of Circulating Red Blood Cells” is available here.
DOI: doi.org/10.1038/s41467-026-71013-x
This story was written by Hailee Munno, CCIL Communications Intern.