Liposome-mediated delivery of ribosome inactivating proteins to cells in vitro.
This study describes the liposome-mediated delivery of toxins to a variety of cells in vitro. Gelonin, a potent inhibitor of protein synthesis from Gelonium multiflorum, was delivered to the cytoplasm of TLX5 lymphoma cells most effectively by phosphatidylserine vesicles. These liposomes were also capable in inhibiting protein synthesis in XC (transformed rat fibroblasts) and phytohaemagglutinin-stimulated CBA mouse lymphocytes. Phosphatidylcholine liposomes had no capacity to deliver their contents to the cytoplasm, but the addition of cholesterol to the vesicle membrane resulted in an increased capacity. Delivery events were enhanced further by the addition of mixed bovine brain gangliosides to the membrane in the ratio 5:5:1 phosphatidylcholine/ cholesterol/gangliosides. The addition of cholesterol to phosphatidylserine vesicles failed to increase the inhibitory effects of the gelonin liposomes. The A chain of diphtheria toxin encapsulated in phosphatidylserine liposomes had no inhibitory effect on the level of protein synthesis in TLX5 or Daudi cells.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000378:metabolism*; D008081:Liposomes; D008214:Lymphocytes / Q000378:metabolism*; D008223:Lymphoma / Q000378:metabolism*; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism; D010718:Phosphatidylserines / Q000494:pharmacology*; D010940:Plant Proteins / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D012156:Reticulocytes / Q000187:drug effects / Q000378:metabolism; D054789:Ribosome Inactivating Proteins, Type 1; D012270:Ribosomes / Q000187:drug effects; D013601:T-Lymphocytes / Q000378:metabolism
D008081:Liposomes; D010718:Phosphatidylserines; D010940:Plant Proteins; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum