The in vitro kinetics of the interactions between PEG-ylated magnetic-fluid-loaded liposomes and macrophages.
Binding and uptake kinetics of magnetic-fluid-loaded liposomes (MFL) by endocytotic cells were investigated in vitro on the model cell-line J774. MFL consisted of unilamellar phosphatidylcholine vesicles (mean hydrodynamic diameter close to 200nm) encapsulating 8-nm nanocrystals of maghemite (gamma-Fe(2)O(3)) and sterically stabilized by introducing 5mol% of distearylphosphatidylcholine poly(ethylene glycol)(2,000) (DSPE-PEG(2,000)) in the vesicle bilayer. The association processes with living macrophages were followed at two levels. On one hand, the lipid vesicles were imaged by confocal fluorescence microscopy. For this purpose 1mol% of rhodamine-marked phosphatidylethanolamine was added to the liposome composition. On the other hand, the iron oxide particles associated with cells were independently quantified by magnetophoresis. All the experiments were similarly performed with PEG-ylated or conventional MFL to point out the role of polymer coating. The results showed cell association with both types of liposomes resulting from binding followed by endocytosis. Steric stabilization by PEG chains reduced binding efficiency limiting the amount of MFL internalized by the macrophages. In contrast, PEG coating did not change the kinetics of endocytosis which exhibited the same first-order rate constant for both conventional and PEG-ylated liposomes. Moreover, lipids and iron oxide particle uptakes were perfectly correlated, indicating that MFL vesicle structure and encapsulation rate were preserved upon cell penetration.
Martina
Marie-Sophie
MS
Equipe Physico-Chimie des Systèmes Polyphasés, CNRS UMR 8612, F-92296 Châtenay-Malabry Cedex, France.
Nicolas
Valerie
V
Wilhelm
Claire
C
Ménager
Christine
C
Barratt
Gillian
G
Lesieur
Sylviane
S
D000818:Animals; D002460:Cell Line; D004705:Endocytosis / Q000502:physiology; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008280:Magnetics; D008422:Materials Testing; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry / Q000378:metabolism*
D008081:Liposomes; D011092:Polyethylene Glycols