Monoclonal antibody targeting of liposomes to mouse lung in vivo.
A monoclonal antibody (MoAb), 273-34A, specifically binds to an epitope expressed almost exclusively on capillary endothelial cells of the lung. Within 15 min after i.v. injection, approximately 80 to 85% of the injected radioiodinated MoAb 273-34A accumulates in the lung. Approximately 90 to 95% of the recovered dose is found in the lung for up to 1 week postinjection. Ratios of MoAb 273-34A to a nonspecific, irrelevant MoAb 135-14 are 250 to 285 times higher in the lung than in the serum. When 273-34A was coupled with palmitic acid and incorporated into liposomes, the amount of 125I-labeled liposomes recovered per g of tissue was 12 times higher in the lung than in the liver at 15 min postinjection, and 22 times higher at 5 h postinjection. At 24 h postinjection the amount of liposomes per gram of lung tissue was still 6.0 times the amount per gram of liver tissue. Liposomes conjugated to MoAb 273-34A locate in the lung 20 and 15 times better than do liposomes conjugated to the nonspecific MoAb 135-14 at 15 min and 24 h postinjection, respectively. The results indicate that this immunoliposome system could be used as a model for enhanced drug delivery to the lung. The potential use for delivering anticancer drugs for therapy of lung tumors is discussed.
Hughes
B J
BJ
Department of Biochemistry, University of Tennessee, Knoxville 37996-0840.
Kennel
S
S
Lee
R
R
Huang
L
L
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D002784:Cholesterol; D004285:Dogs; D004337:Drug Carriers; D004730:Endothelium, Vascular / Q000276:immunology*; D000939:Epitopes / Q000032:analysis*; D006207:Half-Life; D007457:Iodine Radioisotopes; D008081:Liposomes; D008168:Lung / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019308:Palmitic Acid; D010169:Palmitic Acids; D010713:Phosphatidylcholines; D011652:Pulmonary Circulation; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D000939:Epitopes; D007457:Iodine Radioisotopes; D008081:Liposomes; D010169:Palmitic Acids; D010713:Phosphatidylcholines; D019308:Palmitic Acid; D002784:Cholesterol