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Red blood cell (RBC) surface primary amines are chemical functional groups located on the N-termini and lysine side chains of various membrane-spanning proteins, most notably Glycophorin A and Band 3 (Muzykantov, 2010). These amines serve as a critical target for site-specific bioconjugation, allowing for the covalent attachment of therapeutic enzymes, antibodies, or imaging contrast agents (Villa et al., 2016). By anchoring drugs to the RBC surface, the circulatory half-life of the therapeutic payload is significantly extended, often from minutes to weeks, leveraging the natural 120-day lifespan of the erythrocyte (Magnani et al., 2002). This strategy is employed in the development of carrier erythrocytes for treating conditions like acute lymphoblastic leukemia or lysosomal storage disorders (Rossi et al., 2005). However, the modification of these amines can alter the cell's deformability or surface charge, potentially leading to premature clearance by the mononuclear phagocyte system in the spleen (Khamari et al., 2021). Furthermore, the introduction of foreign moieties onto these amines may induce the formation of neoantigens, posing a risk of immune-mediated hemolysis (Muzykantov, 2010). Despite these challenges, RBC surface amines remain a cornerstone of erythrocyte-based drug delivery systems due to their high density and accessibility on the cell exterior.
Covalent acylation or alkylation of primary amine groups on the erythrocyte membrane to anchor therapeutic or diagnostic agents for extended circulation.
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