Functionalization of Liposomes with Hydrophilic Polymers Results in Macrophage Uptake Independent of the Protein Corona

Liposomes
are established drug carriers that are employed to transport
and deliver hydrophilic drugs in the body. To minimize unspecific
cellular uptake, nanocarriers are commonly modified with poly­(ethylene
glycol) (PEG), which is known to minimize unspecific protein adsorption.
However, to date, it has not been studied whether this is an intrinsic
and specific property of PEG or if it can be transferred to hyperbranched
polyglycerol (hbPG) as well. Additionally, it remains
unclear if the reduction of unspecific cell uptake is independent
of the “basic” carrier at which a surface functionalization
with polymers is usually applied. Therefore, we studied the protein
corona of differently functionalized liposomes (unfunctionalized vs
PEG or hbPG-functionalized) using PEGylated and PGylated
lipids. Their cellular uptake in macrophages was compared. For all
three liposomal samples, rather similar protein corona compositions
were found, and alsomore importantlythe total amount
of proteins adsorbed was very low compared to other nanoparticles.
Interestingly, the cellular uptake was then significantly changed
by the surface functionalization itself, despite the adsorption of
a small amount of proteins: although the PEGylation of liposomes resulted
in the abovementioned decreased cell uptake, functionalization with hbPG lead to enhanced macrophage interactionboth
in the media with and without proteins. In comparison to other nanocarrier
systems, this seems to be a liposome-specific effect related to the
low amount of adsorbed proteins.