Optimization of the liposomes encapsulating a new lipopeptide CGP 31362 for efficient activation of tumoricidal properties in monocytes and macrophages.
The purpose of this study was to optimize a suitable liposomal carrier for CGP 31362, a new synthetic lipopeptide analogue of gram-negative bacterial cell walls. CGP 31362 was inserted into the membranes of different liposomes with different phospholipid composition. We determined the ability of these liposomes to activate tumoricidal properties in mouse peritoneal and bone marrow macrophages, and in human monocytes. The ideal liposome carrier for CGP 31362 consisted of phosphatidylcholine and phosphatidylserine in a 7:3 molar ratio. Subsequent to efficient binding and endocytosis, CGP 31362 in liposomes of this composition rendered mouse macrophages and human monocytes highly tumoricidal. Moreover, even in the absence of interferon-gamma, human monocytes released significant levels of tumor necrosis factor and interleukin-1. These data show that in a suitable liposomal carrier, the new synthetic lipopeptide in liposomes is a potent activator of tumoricidal properties in macrophages.
Nii
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Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Utsugi
T
T
Fan
D
D
Denkins
Y
Y
Pak
C
C
Brown
D
D
van Hoogevest
P
P
Fidler
I J
IJ
D000818:Animals; D003602:Cytotoxicity, Immunologic; D015232:Dinoprostone / Q000378:metabolism; D004337:Drug Carriers; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D008081:Liposomes; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D009369:Neoplasms / Q000276:immunology*; D009842:Oligopeptides / Q000008:administration & dosage* / Q000494:pharmacology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology; D010587:Phagocytosis; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004337:Drug Carriers; D007375:Interleukin-1; D008081:Liposomes; D009842:Oligopeptides; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C068423:CGP 31362; D015232:Dinoprostone