Stable target-sensitive immunoliposomes.
Interaction of immunoliposomes composed of dioleoylphosphatidylethanolamine (DOPE) (80%), dioleoylphosphatidic acid (DOPA) (20%), and a small amount of specific antibody with Herpes Simplex virus (HSV) were studied by detecting the immune-dependent lysis of liposomes. DOPA was used as the principal stabilizer of the immunoliposomes. Antibodies conjugated with N-glutarylphosphatidylethanolamine or oxidized GM1 served as the target-specific ligands of immunoliposomes. These immunoliposomes (d = 160-180 nm) were stable for at least one month when stored at 4 degrees C. However, they undergo a rapid aggregation and lysis reaction in the presence of a membrane-bound target such as intact HSV virions. We have also employed epitope peptide-containing liposomes (target liposomes) to mimic the virus and showed that the immunoliposomes could be aggregated and lysed by the target liposomes in an antigen-dependent manner. Immunoliposome lysis could be accelerated by increasing the incubation temperature to 60-70 degrees C. No immunoliposome lysis was observed if the target liposomes were absent, indicating the prolonged stability of the immunoliposomes. Liposome lysis was always accompanied by liposome aggregation. However, the aggregation-induced liposome destabilization is unique to the HII phase-forming lipids such as DOPE. DOPC-containing immunoliposomes did not lyse despite the fact that massive liposome aggregation had taken place.
Department of Biochemistry, University of Tennessee, Knoxville 37996-0840.
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Pinnaduwage
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Huang
D000595:Amino Acid Sequence; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D004337:Drug Carriers; D004355:Drug Stability; D000939:Epitopes / Q000276:immunology; D008051:Lipid Bilayers; D008081:Liposomes / Q000276:immunology*; D008969:Molecular Sequence Data; D010712:Phosphatidic Acids; D010714:Phosphatidylethanolamines; D018139:Simplexvirus / Q000276:immunology*; D013696:Temperature
D000914:Antibodies, Viral; D000956:Antigens, Viral; D004337:Drug Carriers; D000939:Epitopes; D008051:Lipid Bilayers; D008081:Liposomes; D010712:Phosphatidic Acids; D010714:Phosphatidylethanolamines; C037657:dioleoylphosphatidic acid; C020888:1,2-dielaidoylphosphatidylethanolamine