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The streptavidin-biotinylated red blood cell (SA-BioRBC) complex is a specialized drug delivery platform that utilizes the exceptionally high affinity between the bacterial protein streptavidin and the small molecule biotin (Vitamin B7) [1, 2]. In this system, red blood cells (RBCs) are chemically modified to present biotin on their surface, which then serves as an anchor for streptavidin-linked therapeutic cargoes [3]. This approach exploits the natural longevity of erythrocytes in the bloodstream to significantly extend the circulation time of drugs, such as enzymes or antibodies, which would otherwise be rapidly eliminated [1, 4]. While not a therapeutic target in the traditional sense of a disease-causing molecule, the SA-BioRBC system is a critical tool in experimental pharmacology for treating conditions like enzyme deficiencies and vascular thrombosis [3]. The primary mechanism involves the formation of a stable, non-covalent bridge that resists dissociation under physiological conditions [2]. However, the clinical application of this technology is challenged by the potential immunogenicity of streptavidin, which can lead to the formation of neutralizing antibodies and rapid clearance of the delivery vehicle [1, 3]. Additionally, excessive surface modification of the RBCs can lead to hemolysis or premature removal by the spleen and liver [4]. [1] Muzykantov VR. Drug delivery by red blood cells: vascular carriers designed by mother nature. Expert Opin Drug Deliv. 2010;7(4):403-427. [2] Green NM. Avidin. Adv Protein Chem. 1975;29:85-133. [3] Villa CH, Anselmo AC, Mitragotri S, Muzykantov V. Red blood cells: Super-carriers for drugs, biologicals, and nanoparticles and biologicals. Adv Drug Deliv Rev. 2016;106(Pt A):88-103. [4] Magnani M, Rossi L, Fraternale A, et al. Erythrocyte-mediated delivery of drugs, peptides and nucleic acids. Gene Ther. 2002;9(11):749-751.
High-affinity non-covalent binding of streptavidin to biotinylated surfaces to anchor therapeutic cargoes to long-circulating erythrocytes.
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