Highly efficient immunoliposomes prepared with a method which is compatible with various lipid compositions.
Monoclonal antibody was conjugated to N-glutaryl-phosphatidylethanolamine in the presence of octylglucoside by using N-hydroxysulfosuccinimide as a carboxyl-activation reagent. The conjugated antibody was then incorporated into liposomes by a simple dialysis method. The method is mild and is compatible with various lipid compositions of the liposomes. We have prepared immunoliposomes containing a lung endothelium-specific monoclonal antibody and showed excellent target binding (approximately 75% injected dose) of the immunoliposomes in mouse. Immunoliposomes can be prepared to contain other acidic lipids such as phosphatidylserine and various amounts of cholesterol. The presence of 20% or more cholesterol in liposomes resulted in high level of target binding. We have used in these experiments a new radioactive lipid-phase marker, 111In-DTPA-SA, which was very stable in vivo. The halflife of clearance in mouse exceeded 3 weeks.
Holmberg
E
E
Department of Biochemistry, University of Tennessee, Knoxville 37996.
Maruyama
K
K
Litzinger
D C
DC
Wright
S
S
Davis
M
M
Kabalka
G W
GW
Kennel
S J
SJ
Huang
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002784:Cholesterol / Q000032:analysis; D004727:Endothelium / Q000276:immunology; D007205:Indium Radioisotopes; D007700:Kinetics; D008081:Liposomes; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D004369:Pentetic Acid; D010713:Phosphatidylcholines / Q000032:analysis; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines / Q000032:analysis; D051381:Rats; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D008081:Liposomes; C049392:N-glutarylphosphatidylethanolamine; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D004369:Pentetic Acid; D002784:Cholesterol