Receptor versus non-receptor mediated clearance of liposomes

Numerous studies have appeared over the years dealing with liposome-cell interaction mechanisms, most of them performed under in vitro conditions with isolated cell populations or cell lines. It is remarkable that, nonetheless, there hardly seem to exist established and generally accepted views on how precisely liposomes interact with cells and by what parameters this is influenced. In this article we will summarize and discuss the most relevant studies (in our opinion) on this matter in relation to in vivo conditions and with special attention to the relation between scavenger, complement and PS receptors.Researchers in the field have long been aware of the interaction of liposomes with blood proteins and their potential involvement in the process of liposome elimination from the blood circulation. A few of these 'opsonizing' proteins have been identified, but it is not clear to what extent each of them determines the fate of the liposome in the blood stream and how liposomal parameters such as size, charge and rigidity play a role in this process. We will include in this article our own recent observations on a thus far largely ignored class of such liposomal 'opsonins', the apolipoproteins. This class of plasma proteins, which physiologically are instrumental in hepatic lipoprotein clearance and processing, has been shown to contribute specifically to hepatocyte-mediated uptake of liposomes.Separately, as opposed to the fate of plain liposomes, we briefly touch on the clearance of surface-modified liposomes, which are designed to actively target specific cells or tissues. Plasma proteins are not usually supposed to play a significant role in the clearance of such liposomes. We will summarize these studies and address in this connection the question of how plasma proteins may interfere with such active targeting attempts.