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<p>Engineering red blood cells (RBCs) has been widely explored for drug delivery, imaging, vaccination, and other applications. However, effective strategies to directly engineer RBCs in vivo are still lacking. Here, we report successful metabolic glycan labeling of RBCs in vivo. We demonstrate that systemically administered azido-sugars can metabolically label circulating RBCs with azido groups, through labeling of both mature RBCs and RBC precursor cells. The surface azido tags on RBCs can persist for over 42 days in female mice (nearly the lifespan of RBCs), while tags on leukocytes decay to negligible levels within 3 days. Azido-labeled RBCs can covalently capture dibenzocyclooctyne-bearing cargos in vivo via click chemistry, extending cargo circulation from hours to over 35 days. This RBC tagging and targeting technology can improve fluorescence imaging of blood vessels, enable long-term MRI of brain vasculatures with a single gadolinium dose, and improve the pharmacokinetics of drugs.</p>

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In vivo metabolic tagging and targeting of circulating red blood cells

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月21日

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  • Yusheng Liu,
  • Yizun Wang,
  • Kyungwon Ko,
  • Yuan Liu,
  • Haiyi Huang,
  • Yueji Wang,
  • Jiadiao Zhou,
  • Dhyanesh Baskaran,
  • Joonsu Han,
  • Rimsha Bhatta,
  • Daniel Nguyen,
  • Cecilia Leal,
  • Matthew R. Berry,
  • Fan Lam,
  • Hua Wang

摘要

Engineering red blood cells (RBCs) has been widely explored for drug delivery, imaging, vaccination, and other applications. However, effective strategies to directly engineer RBCs in vivo are still lacking. Here, we report successful metabolic glycan labeling of RBCs in vivo. We demonstrate that systemically administered azido-sugars can metabolically label circulating RBCs with azido groups, through labeling of both mature RBCs and RBC precursor cells. The surface azido tags on RBCs can persist for over 42 days in female mice (nearly the lifespan of RBCs), while tags on leukocytes decay to negligible levels within 3 days. Azido-labeled RBCs can covalently capture dibenzocyclooctyne-bearing cargos in vivo via click chemistry, extending cargo circulation from hours to over 35 days. This RBC tagging and targeting technology can improve fluorescence imaging of blood vessels, enable long-term MRI of brain vasculatures with a single gadolinium dose, and improve the pharmacokinetics of drugs.