Receptor-mediated endocytosis of poly(acrylic acid)-conjugated liposomes by macrophages
Abstract
The uptake characteristics of negatively-charged liposomes made by conjugation of poly(acrylic acid) (PAA) were studied with respect to cultured RAW macrophages. The PAA-conjugated liposomes were internalized and digested in an acidic compartment at a much faster rate than the unmodified phosphatidylcholine (PC) liposomes. After incubation for 18 h, an over 5-fold increase in the uptake of PC liposomes was obtained by PAA conjugation. Subsequently, part of the aqueous phase of the internalized liposomes was exocytosed. Recognition of PAA by the macrophages seems to be responsible for the enhanced uptake of PAA-conjugated liposomes. Cross-competition experiments showed that PAA-conjugated liposomes inhibited the uptake of acetylated-low density lipoprotein (acetyl-LDL) by the macrophages and vice versa. The uptake of PAA-conjugated liposomes was also inhibited by dextran sulfate and maleylated-bovine serum albumin (maleyl-BSA), which are also known to bind to scavenger receptors. Poly(C) and BSA, which are not ligands for the scavenger receptor, competed poorly with the uptake of PAA-conjugated liposomes. Enhanced uptake of PAA-conjugated liposomes by CHO cells with low scavenger receptor expression was not observed. Unexpectedl...Continue Reading
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