Monensin intercalation in liposomes: effect on cytotoxicities of ricin, Pseudomonas exotoxin A and diphtheria toxin in CHO cells.
Monensin, a carboxylic ionophore was intercalated in liposomes (liposomal monensin) and its effect on cytotoxicities of ricin, Pseudomonas exotoxin A and diphtheria toxin in CHO cells was studied. Intercalation of monensin in liposomal bilayer is found to have no effect on its stability and interaction with cells. Liposomal monensin (1 nM) substantially enhance the cytotoxicities of ricin (62-fold) and Pseudomonas exotoxin A (11.5-fold) while it has no effect on diphtheria toxin. This observed effect is highly dependent on the liposomal lipid composition. The potentiating ability of monensin (1 nM) in neutral vesicles is significantly higher (2.2-fold) as compared to negatively charges vesicles. This ability is drastically reduced by incorporation of stearylamine in liposomes and is found to be dependent on the density of stearylamine as well as on the concentration of serum in the medium. Monensin in liposomes containing 24 mol% stearylamine has a very marginal effect on the cytotoxicity of ricin (7.5-fold) which is further reduced (1.5-fold) in the presence of 20% serum. The uptake of 125I-gelonin from neutral vesicles is significantly higher (approximately 2.0-fold) than that from the negative vesicles. The uptake from positive vesicles is highly dependent on the concentration of stearylamine. The reduction in the lag period (30 min) of ricin action by monensin in neutral and negative vesicle is comparable with free monensin. However, monensin in positive vesicle has no effect on it. These studies have suggested that liposomes could be used as a delivery vehicle for monensin for selective elimination of tumor cells in combination with hybrid toxins.
Madan
S
S
Department of Biochemistry, University of Delhi, India.
Ghosh
P C
PC
D036002:ADP Ribose Transferases; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D001692:Biological Transport; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects*; D002784:Cholesterol; D006224:Cricetinae; D004167:Diphtheria Toxin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005098:Exotoxins / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007700:Kinetics; D008081:Liposomes; D008985:Monensin / Q000008:administration & dosage / Q000494:pharmacology*; D010713:Phosphatidylcholines; D010940:Plant Proteins / Q000378:metabolism*; D011500:Protein Synthesis Inhibitors / Q000378:metabolism*; D054789:Ribosome Inactivating Proteins, Type 1; D012276:Ricin / Q000633:toxicity*; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D002784:Cholesterol; D004167:Diphtheria Toxin; D004337:Drug Carriers; D005098:Exotoxins; D007457:Iodine Radioisotopes; D008081:Liposomes; D008985:Monensin; D010713:Phosphatidylcholines; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D054789:Ribosome Inactivating Proteins, Type 1; D012276:Ricin; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C025674:GEL protein, Gelonium multiflorum