Surface-associated serum proteins inhibit the uptake of phosphatidylserine and poly(ethylene glycol) liposomes by mouse macrophages.
Serum proteins, acting as opsonins, are believed to contribute significantly to liposome-macrophage cell association and thus regulate liposome uptake by cells of the mononuclear phagocytic system (MPS). We studied the effect of serum protein on binding and uptake of phosphatidylglycerol-, phosphatidylserine-, cardiolipin-, and N,N-dioleyl-N,N-dimethylammonium chloride- (DODAC) containing as well as poly(ethylene glycol)- (PEG) containing liposomes by mouse bone marrow macrophages in vitro. Consistent with the postulated surface-shielding properties of PEG, protein-free uptake of liposomes containing 5 mol% PEG and either 20 mol% anionic phosphatidylserine or 20 mol% cationic DODAC was equivalent to uptake of neutral liposomes. In contrast to previous reports indicating that protein adsorption to liposomes increases uptake by macrophages, the presence of bound serum protein did not increase the uptake of these liposomes by cultured macrophages. Rather, we found that pre-incubating liposomes with serum reduced the uptake of liposomes containing phosphatidylserine. Surprisingly, serum treatment of PEG-containing liposomes also significantly reduced liposome uptake by macrophages. It is postulated that, in the case of phosphatidylserine liposomes, the bound serum protein can provide a non-specific surface-shielding property that reduces the charge-mediated interactions between liposomes and bone marrow macrophage cells. In addition, incubation of PEG-bearing liposomes with serum can result in a change in the properties of the PEG, resulting in a surface that is better protected against interactions with cells.
Johnstone
S A
SA
Division of Medical Oncology - Advanced Therapeutics, British Columbia Cancer Agency, 600 West 10th Avenue, Vancouver, B.C., Canada V5Z 4E6. sjohnsto@bccancer.br.ca
Masin
D
D
Mayer
L
L
Bally
M B
MB
D000818:Animals; D001769:Blood; D001798:Blood Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D001854:Bone Marrow Cells; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D005591:Chemical Fractionation; D004337:Drug Carriers; D004591:Electrophoresis, Polyacrylamide Gel; D008081:Liposomes / Q000737:chemistry; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008968:Molecular Conformation; D010587:Phagocytosis; D010718:Phosphatidylserines / Q000378:metabolism*; D011092:Polyethylene Glycols; D011485:Protein Binding
D001798:Blood Proteins; D004337:Drug Carriers; D008081:Liposomes; D010718:Phosphatidylserines; D011092:Polyethylene Glycols