Involvement of scavenger receptor class B type 1 and low-density lipoprotein receptor in the internalization of liposomes into HepG2 cells

In this study, HepG2 cells, an in vitro model system for human hepatocytes, were used to evaluate the interaction of lipoprotein receptors with liposomes carrying fluorescently labeled cholesterol and their subsequent intracellular uptake. In these experiments, two lipoprotein receptors, scavenger receptor class B type 1 (SR-B1) and low-density lipoprotein receptor (LDLR), accounted for approximately 20% and 10%, respectively, of the intracellular uptake of the labeled liposomes. These findings indicate that additional mechanisms contributed to liposomal internalization. Liposomes modified with both apolipoproteins A-I and E were internalized in HepG2 cells in FBS-depleted culture medium at the same levels as unmodified liposomes in FBS-containing culture medium, which indicates that apolipoproteins A-I and E were the major serum components involved in liposomal binding to SR-B1 or LDLR (or both). These results increase our understanding of the disposition of liposomes, processes that can directly affect the efficacy and safety of drug products. [Display omitted] •We used fluorescent NBD-Chol-liposomes to study liposomal transit into hepatocytes.•SR-B1 and LDLR participated in liposome uptake by HepG2 cells.•Apolipoprotein A-I and E mediated the interactions among SR-B1, LDLR, and liposomes.