Avidin-induced lysis of biotinylated erythrocytes by homologous complement via the alternative pathway depends on avidin's ability of multipoint binding with biotinylated membrane

Muzykantov, Vladimir R.; Smirnov, Mikhail D.; Samokhin, Gennady P.

doi:10.1016/0005-2736(92)90336-k

Cited by 19 publications

(15 citation statements)

References 15 publications

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“…It has also been found in late eighties that excessive cross-linking of biotinylated RBC membrane by avidin, streptavidin or neutravidin, all of which have four high-affinity binding sites for biotin and thereby serve for coupling biotinylated molecules to RBC, causes to RBC lysis by complement activated via the alternative pathway27,175, leading to intravascular hemolysis and rapid elimination of modified RBC176. Studies of the molecular mechanisms of this phenomenon revealed that modification of RBC membrane glycoproteins Decay Acceleration Factor (DAF) and CD59 (that suppress complement activation and assembly of membrane-attacking complex in RBC membrane, respectively), is responsible for this unwanted side effect56,177,178. This allowed design of non-damaging means for coupling of molecules to RBC via biotin-avidin cross-linker without loss of RBC biocompatibility159,179; thus RBC carrying up to 10 5 molecules of protein cargo conjugated via streptavidin in a biocompatible manner circulate in animals similarly to naïve RBC, without enhanced clearance, lysis or organ uptake180,181.…”

Section: Coupling Therapeutics To the Rbc Surfacementioning

confidence: 99%

“…However, until recently, no attempts to test these drug delivery systems in animal models have been reported, presumably because conjugation of drugs grossly compromised RBC biocompatibility. In particular, inactivation of complement inhibitors DAF and CD59 in RBC membrane257 led to hemolysis, phagocytosis and rapid elimination of RBC27,175–178,258. Eventually, methods to couple up to ~10 5 copies of therapeutic proteins per RBC without RBC damage have been devised 150,159,163,179,180.…”

Section: Coupling Therapeutics To the Rbc Surfacementioning

confidence: 99%

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Drug delivery by red blood cells: vascular carriers designed by mother nature

Muzykantov

2010

Expert Opinion on Drug Delivery

346

294

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Importance of the field-Vascular delivery of several classes of therapeutic agents may benefit from carriage by red blood cells (RBC), for example, drugs that require delivery into phagocytic cells and those that must act within the vascular lumen. The fact that several protocols of infusion of RBCencapsulated drugs are been currently explored in patients illustrates a high biomedical importance for the field.Areas covered by this review-Two strategies for RBC drug delivery are discussed: encapsulation into isolated RBC ex vivo followed by infusion in compatible recipients and coupling therapeutics to surface of RBC. Studies of pharmacokinetics and effects in animal models and in human studies of diverse therapeutic enzymes, antibiotics and other drugs encapsulated in RBC are described and critically analyzed. Coupling to RBC surface of compounds regulating immune response and complement, affinity ligands, polyethylene glycol alleviating immune response to donor RBC and fibrinolytic plasminogen activators is d escribed. Also described is a novel, translation-prone approach for RBC drug delivery by injecting of therapeutics conjugated with fragments of antibodies providing safe anchoring of cargoes to circulating RBC, without need for ex vivo modification and infusion of RBC.What the reader will gain-The readers will gain historical perspective, current status, challenges and perspectives of medical applications of RBC for drug delivery.Take home message-RBC represent naturally designed carriers for intravascular drug delivery, characterized by unique longevity in the bloodstream, biocompatibility and safe physiological mechanisms for metabolism. Novel approaches for encapsulating drugs into RBC and coupling to RBC surface provide promising avenues for safe and widely useful improvement of drug delivery in the vascular system.

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Section: Coupling Therapeutics To the Rbc Surfacementioning

confidence: 99%

Section: Coupling Therapeutics To the Rbc Surfacementioning

confidence: 99%

Drug delivery by red blood cells: vascular carriers designed by mother nature

Muzykantov

2010

Expert Opinion on Drug Delivery

346

294

View full text Add to dashboard Cite

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“…This is, however, often a result of heavy modifications to the RBC surface. The longevity of modified RBC depends on numerous mechanisms and has been studied in detail 37–40. However, a key factor for the biocompatibility is the resilience of the hybrid liposomes against mechanical stress.…”

Section: Discussionmentioning

confidence: 99%

“…The longevity of modified RBC depends on numerous mechanisms and has been studied in detail. [37][38][39][40] However, a key factor for the biocompatibility is the resilience of the hybrid liposomes against mechanical stress. Figure S5, Supporting Information, shows the result of a lysis assay where hybrid liposomes containing 20% DMPC were exposed to increasing osmotic stress by altering the molar concentration of a phosphate buffer saline.…”

Section: Discussionmentioning

confidence: 99%

Hybrid Erythrocyte Liposomes: Functionalized Red Blood Cell Membranes for Molecule Encapsulation

et al. 2020

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The modification of erythrocyte membrane properties provides a new tool towards improved drug delivery and biomedical applications. The fabrication of hybrid erythrocyte liposomes is presented by doping red blood cell membranes with synthetic lipid molecules of different classes (PC, PS, PG) and different degrees of saturation (14:0, 16:0–18:1). The respective solubility limits are determined, and material properties of the hybrid liposomes are studied by a combination of X‐ray diffraction, epi‐fluorescent microscopy, dynamic light scattering (DLS), Zeta potential, UV‐vis spectroscopy, and Molecular Dynamics (MD) simulations. Membrane thickness and lipid orientation can be tuned through the addition of phosphatidylcholine lipids. The hybrid membranes can be fluorescently labelled by incorporating Texas‐red DHPE, and their charge modified by incorporating phosphatidylserine and phosphatidylglycerol. By using fluorescein labeled dextran as an example, it is demonstrated that small molecules can be encapsulated into these hybrid liposomes.

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“…Development of more precisely controlled conjugation methods [104,110,122–124], preserving DAF and CD59 and avoiding activation of complement [60,124–125] permitted coupling of drugs to RBCs with less damage. The circulation of RBC/drug complexes approximated those of control RBCs for at least several days after injection in rats and mice [122,126].…”

Section: Coupling Therapeutics To the Rbc Surface: Prototype Studiesmentioning

confidence: 99%

Delivery of Drugs Bound to erythrocytes: New Avenues for an Old Intravascular Carrier

et al. 2015

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For several decades, researchers have used erythrocytes for drug delivery of a wide variety of therapeutics in order to improve their pharmacokinetics, biodistribution, controlled release and pharmacodynamics. Approaches include encapsulation of drugs within erythrocytes, as well as coupling of drugs onto the red cell surface. This review focuses on the latter approach, and examines the delivery of red blood cell (RBC)-surface-bound anti-inflammatory, anti-thrombotic and anti-microbial agents, as well as RBC carriage of nanoparticles. Herein, we discuss the progress that has been made in surface loading approaches, and address in depth the issues relevant to surface loading of RBC, including intrinsic features of erythrocyte membranes, immune considerations, potential surface targets and techniques for the production of affinity ligands.

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Avidin-induced lysis of biotinylated erythrocytes by homologous complement via the alternative pathway depends on avidin's ability of multipoint binding with biotinylated membrane

Cited by 19 publications

References 15 publications

Drug delivery by red blood cells: vascular carriers designed by mother nature

Drug delivery by red blood cells: vascular carriers designed by mother nature

Hybrid Erythrocyte Liposomes: Functionalized Red Blood Cell Membranes for Molecule Encapsulation

Delivery of Drugs Bound to erythrocytes: New Avenues for an Old Intravascular Carrier

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