Cytotoxicity of diphtheria toxin A fragment to toxin-resistant murine cells delivered by pH-sensitive immunoliposomes. 1987

D Collins, and L Huang

pH-sensitive immunoliposomes composed of dioleoylphosphatidylethanolamine and oleic acid (8:2 molar ratio) mediated the delivery of the cytotoxic fragment A of diphtheria toxin to the cytoplasm of target L-929 cells. Free fragment A, fragment A encapsulated in antibody-free liposomes, or fragment A encapsulated in pH-insensitive immunoliposomes was not effective in the inhibition of the cellular protein synthesis. pH-sensitive immunoliposomes containing diphtheria fragment A were not toxic to nontarget diphtheria-resistant A31 cells or to nontarget diphtheria-sensitive Vero cells. Pretreatment of target L-929 cells with the weak bases NH4Cl or chloroquine, agents which raise the endosome/lysosome pH, blocked the cytotoxic effect of the pH-sensitive immunoliposomes containing fragment A. Excess free antibody or excess empty pH-sensitive immunoliposomes also blocked the cytotoxic effect. Since it is known that fragment A alone cannot cross lipid membranes, the results of this study indicate that pH-sensitive immunoliposomes are able to release the toxin into the cytoplasm, probably by fusing with the endosome membrane following a receptor-mediated endocytosis of the immunoliposome.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D007739 L Cells A cultured line of C3H mouse FIBROBLASTS that do not adhere to one another and do not express CADHERINS. Earle's Strain L Cells,L Cell Line,L Cells (Cell Line),L-Cell Line,L-Cells,L-Cells, Cell Line,L929 Cell Line,L929 Cells,NCTC Clone 929 Cells,NCTC Clone 929 of Strain L Cells,Strain L Cells,Cell Line L-Cell,Cell Line L-Cells,Cell Line, L,Cell Line, L929,Cell Lines, L,Cell, L,Cell, L (Cell Line),Cell, L929,Cell, Strain L,Cells, L,Cells, L (Cell Line),Cells, L929,Cells, Strain L,L Cell,L Cell (Cell Line),L Cell Lines,L Cell, Strain,L Cells, Cell Line,L Cells, Strain,L-Cell,L-Cell Lines,L-Cell, Cell Line,L929 Cell,Strain L Cell
D008081 Liposomes Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. Niosomes,Transferosomes,Ultradeformable Liposomes,Liposomes, Ultra-deformable,Liposome,Liposome, Ultra-deformable,Liposome, Ultradeformable,Liposomes, Ultra deformable,Liposomes, Ultradeformable,Niosome,Transferosome,Ultra-deformable Liposome,Ultra-deformable Liposomes,Ultradeformable Liposome
D009829 Oleic Acids A group of fatty acids that contain 18 carbon atoms and a double bond at the omega 9 carbon. Octadecenoic Acids,Acids, Octadecenoic,Acids, Oleic
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010714 Phosphatidylethanolamines Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to an ethanolamine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and ethanolamine and 2 moles of fatty acids. Cephalin,Cephalins,Ethanolamine Phosphoglyceride,Ethanolamine Phosphoglycerides,Ethanolamineglycerophospholipids,Phosphoglyceride, Ethanolamine,Phosphoglycerides, Ethanolamine
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004167 Diphtheria Toxin An ADP-ribosylating polypeptide produced by CORYNEBACTERIUM DIPHTHERIAE that causes the signs and symptoms of DIPHTHERIA. It can be broken into two unequal domains: the smaller, catalytic A domain is the lethal moiety and contains MONO(ADP-RIBOSE) TRANSFERASES which transfers ADP RIBOSE to PEPTIDE ELONGATION FACTOR 2 thereby inhibiting protein synthesis; and the larger B domain that is needed for entry into cells. Corynebacterium Diphtheriae Toxin,Toxin, Corynebacterium Diphtheriae
D006863 Hydrogen-Ion Concentration The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH pH,Concentration, Hydrogen-Ion,Concentrations, Hydrogen-Ion,Hydrogen Ion Concentration,Hydrogen-Ion Concentrations

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