Interference of macrophages with immunotargeting of liposomes.
We investigated the binding, uptake and intracellular degradation of immunoliposomes by isolated rat liver macrophages in vitro. Immunoliposomes were prepared either by coupling a randomly thiolated anti-CC531 rat colon adenocarcinoma monoclonal antibody to bilayer-incorporated MPB-PE by means of a thioether linkage or by attaching it through its Fc moiety to the distal terminus of hydrazide-modified PEG-DSPE. The two immunoliposome preparations clearly differ in their interaction with the tumor target cells, as well as with the macrophages. At comparable antibody densities both cell types show 1.5-2-fold higher levels of association for the Hz-PEG-immunoliposomes than for the MPB-PEG-immunoliposomes. We provide evidence that immunoliposome macrophage-interaction is both Fc-receptor and scavenger receptor mediated to about equal extents. At low antibody density the hydrazide immunoliposomes favor interaction with the tumor cells to that with macrophages. At higher antibody densities, on the other hand, interaction of these liposomes with the macrophages is increasingly favored, mostly due to enhanced scavenger receptor mediated uptake. The rate of intracellular degradation of (immuno)liposomes internalized by liver macrophages is barely influenced by the presence of either PEG or immunoglobulins on the liposomal surface.
Koning
Gerben A
GA
Department of Cell Biology, section Liposome Research, Groningen University Institute for Drug Exploration, The Netherlands.
Kamps
Jan A A M
JA
Scherphof
Gerrit L
GL
D000818:Animals; D004305:Dose-Response Relationship, Drug; D050356:Lipid Metabolism; D008055:Lipids / Q000494:pharmacology; D008081:Liposomes / Q000276:immunology* / Q000378:metabolism* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D013997:Time Factors; D014407:Tumor Cells, Cultured
D008055:Lipids; D008081:Liposomes; D011092:Polyethylene Glycols