Fc-receptor-mediated targeting of antibody-bearing liposomes containing dideoxycytidine triphosphate to human monocyte/macrophages.
Liposomes bearing surface-attached antibody (L-Ab) molecules can be used for various purposes including the immunospecific delivery of drugs or other materials to antigenic target cells. In this study, L-Ab were prepared to deliver an anti-human immunodeficiency virus (HIV) drug, dideoxycytidine triphosphate (ddCTP) to human monocyte/macrophages. Cells of the monocyte/macrophage lineage are an important reservoir of HIV-1. A mouse monoclonal antibody IgG2a was labelled with 125I and modified using N succinimidyl-3-(2-pyridyldithio)propionate (SPDP) as a heterobifunctional reagent in order to conjugate with liposomes to produce a covalent bond (thioether). SPDP-modified antibody was incubated with liposomes containing 5 mol% of maleimido phenyl butyrate phosphatidylethanolamine (MPB-PE) at room temperature (21 degrees C) for 24 h. L-Ab were separated from free and aggregated antibodies by centrifugation. L-Ab were characterized by measuring particle size and binding to anti-mouse IgG-sepharose. Ninety five per cent of the liposomal (L-Ab) lipid label was bound to anti-mouse IgG-sepharose, whereas only 7% of plain liposomes were bound, indicating non-specific binding. Uptake of L-Ab was measured in human monocyte/macrophages as a function of time and compared with that of plain liposomes. The uptake increased with time and it was 4-6 times greater than that of plain liposomes although part of that effect may have been due to unreacted MPB groups.
Betageri
G V
GV
National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Black
C D
CD
Szebeni
J
J
Wahl
L M
LM
Weinstein
J N
JN
D000911:Antibodies, Monoclonal / Q000276:immunology*; D003845:Deoxycytosine Nucleotides / Q000008:administration & dosage*; D054306:Dideoxynucleotides; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008081:Liposomes; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*; D013388:Succinimides / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D003845:Deoxycytosine Nucleotides; D054306:Dideoxynucleotides; D007457:Iodine Radioisotopes; D008081:Liposomes; D011961:Receptors, Fc; D013388:Succinimides; C018151:N-succinimidyl 3-(2-pyridyldithio)propionate; C037406:2',3'-dideoxycytidine 5'-triphosphate