Target-sensitive immunoerythrocytes: interaction of biotinylated red blood cells with immobilized avidin induces their lysis by complement.
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.
Muzykantov
V R
VR
Institute of Experimental Cardiology, Russian National Cardiology Research Center, Moscow.
Zaltsman
A B
AB
Smirnov
M D
MD
Samokhin
G P
GP
Morgan
B P
BP
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
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