title: Target-sensitive immunoerythrocytes: interaction of biotinylated red blood cells with immobilized avidin induces their lysis by complement.
abstract: Red blood cells (RBC) coated with antibody (immunoerythrocytes) may be useful for drug targeting. Previously we have developed a methodology for avidin (streptavidin)-mediated attachment of biotinylated antibodies (b-Ab) to biotinylated RBC (B-RBC). We have observed that binding of avidin to B-RBC in suspension leads to their complement-mediated lysis by autologous serum. In the present work we have studied the interaction of B-RBC, which are not complement susceptible, with immobilized avidin and their consequent susceptibility to lysis by complement. B-RBC adhered tightly to avidin-coated surfaces and were rendered susceptible to lysis by autologous serum. A long biotin ester provided more effective binding of the B-RBC to immobilized avidin and greater lysis by complement, than a short biotin ester. Based on these results, we have hypothesized that targeting of serum-stable drug-loaded B-RBC attained by step-wise administration of b-Ab and streptavidin may provide target-sensitive lysis of B-RBC. To confirm this hypothesis, we have studied b-Ab and streptavidin mediated targeting of B-RBC to immobilized antigen. Step-wise addition of biotinylated antibody, avidin or streptavidin and b-RBC caused specific binding of B-RBC to immobilized antigen and their subsequent lysis by autologous serum. Therefore, our results obtained in an in vitro model demonstrate that B-RBC might be used for targeting and local release of drug.
authors.affiliation: Institute of Experimental Cardiology, Russian National Cardiology Research Center, Moscow.
authors.forename: V R
authors.initials: VR
authors.lastname: Muzykantov
authors.forename: A B
authors.initials: AB
authors.lastname: Zaltsman
authors.forename: M D
authors.initials: MD
authors.lastname: Smirnov
authors.forename: G P
authors.initials: GP
authors.lastname: Samokhin
authors.forename: B P
authors.initials: BP
authors.lastname: Morgan
mesh_terms: D000614:Aminocaproates; D000941:Antigens; D001360:Avidin; D001426:Bacterial Proteins; D001710:Biotin / Q000031:analogs & derivatives; D001769:Blood; D018914:Cells, Immobilized; D003165:Complement System Proteins / Q000502:physiology*; D004337:Drug Carriers; D004912:Erythrocytes / Q000737:chemistry / Q000276:immunology*; D006461:Hemolysis; D006801:Humans; D007074:Immunoglobulin G; D019809:Streptavidin; D013388:Succinimides
chemical_list: D000614:Aminocaproates; D000941:Antigens; D001426:Bacterial Proteins; D004337:Drug Carriers; D007074:Immunoglobulin G; D013388:Succinimides; C033788:biotinyl N-hydroxysuccinimide ester; D001360:Avidin; D001710:Biotin; C048592:biotinyl-6-aminocaproic acid N-hydroxysuccinimide ester; D003165:Complement System Proteins; D019809:Streptavidin