Researchers have developed a new method to tag red blood cells inside the body, allowing them to carry drugs and imaging agents for extended periods, according to a study published on Mar. 23 in Nature Communications.
The findings are important because they suggest a safer and more efficient way to deliver therapies or conduct vascular imaging without the need for extracting, manipulating, and reinfusing blood cells—a process that is currently time-consuming, costly, and can pose risks of cell damage or infection.
In this preclinical study using mouse models, scientists injected specialized azido-sugars into the bloodstream. These sugars attached chemical 'hooks' onto circulating red blood cells (RBCs) through metabolic glycan labeling. The tags remained on RBCs for over 42 days—almost their entire lifespan in mice—and allowed subsequent attachment of imaging agents or drugs using click chemistry techniques. The researchers found that about 10-15% of all circulating RBCs were successfully labeled after treatment. While these tags initially appeared on other cell types as well, they faded from white blood cells (WBCs) and non-target tissues within three days but persisted much longer on RBCs.
The technique enabled enhanced medical imaging: attaching gadolinium (Gd) contrast agents to tagged RBCs allowed brain vessel MRI scans for over 11 days with just one dose—a significant improvement over traditional contrast agents that clear within minutes. When insulin was attached to tagged RBCs in diabetic mice, it stayed in circulation longer than standard injections and improved glucose control during testing.
Safety tests showed no changes in cell shape or key metabolic markers such as ATP levels; there was also no evidence of tissue toxicity or changes in blood counts among treated animals. This suggests the approach is safe in preclinical mammalian models so far.
Although this research has only been conducted with mice so far, the authors noted human RBCs live roughly three times longer than those of mice. This could mean even greater durability if adapted for humans—though further work is needed before clinical trials can begin.
