Stealth monensin immunoliposomes as potentiator of immunotoxins in vitro.
Stealth monensin liposomes (SML) were prepared using dipalmitoyl phosphatidylcholine, cholesterol, distearoyl glycerophosphoethanolamine coupled to polyethylene glycol, stearylamine, and N-succinimidyl pyridodithiopropionate linked to stearyl amine, in the molar ratio of 10:5:1.4:1.4:1.5. SML was conjugated to the anti-MY9 antibody by a disulfide linkage to form stealth monensin immunoliposomes (SMIL) by an already established procedure. The encapsulation concentrations of monensin in SML and SMIL were 10(-7) and 4.9x10(-8) M, respectively. More than 20% of monensin remained in circulation after 24 h in BALB/c mice. The ability of SML and SMIL to potentiate the effect of anti-MY9 immunotoxin (anti-MY9-IT) was tested against human leukemia HL-60 sensitive and resistant tumor cells in vitro. SML and SMIL potentiated the activity of anti-MY9-IT by 10-20 times against HL-60 sensitive tumor cell lines. However, greater potentiation of anti-MY9-IT was observed in combination with SML and SMIL against HL-60 resistant tumor cells, found to be 200 and 500 times, respectively. The potentiation of anti-MY9-IT by SMIL was more than two-fold compared with SML against both HL-60 sensitive and resistant tumor cells. Transmission electron microscopy studies conducted with HL-60 resistant cells incubated with anti-MY9-IT and monensin liposomes showed significant dilation of the golgi, which was reversible after re-incubation in fresh medium. Our studies show that SML and SMIL can be successfully used to potentiate the activity of ricin based anti-MY9-IT in vitro, and further in vivo studies will demonstrate the usefulness of this approach.
Singh
M
M
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307-3800, USA. mandip.sachdeva@famu.edu
Ferdous
A J
AJ
Kanikkannan
N
N
Faulkner
G
G
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D002626:Chemistry, Pharmaceutical; D004357:Drug Synergism; D018922:HL-60 Cells; D006207:Half-Life; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage*; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D008855:Microscopy, Electron, Scanning; D008985:Monensin / Q000008:administration & dosage*; D012276:Ricin / Q000008:administration & dosage*
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D008081:Liposomes; D012276:Ricin; D008985:Monensin