Interplay of protein corona and immune cells controls blood residency of liposomes

TLDR

In vivo liposomes acquire a new biological identity through protein corona formation, a dynamic interface that modulates their interaction with the physiological environment. The study aims to critically assess key concepts of liposome technology that must be reviewed for definitive clinical translation. The biological identity of liposomes is linked to their sequestration by peripheral blood mononuclear cells, leading to removal from circulation; pre‑coating with an artificial corona of human plasma proteins markedly reduces leukocyte capture and may prolong in vivo circulation.

Abstract

Abstract In vivo liposomes, like other types of nanoparticles, acquire a totally new ‘biological identity’ due to the formation of a biomolecular coating known as the protein corona that depends on and modifies the liposomes’ synthetic identity. The liposome–protein corona is a dynamic interface that regulates the interaction of liposomes with the physiological environment. Here we show that the biological identity of liposomes is clearly linked to their sequestration from peripheral blood mononuclear cells (PBMCs) of healthy donors that ultimately leads to removal from the bloodstream. Pre-coating liposomes with an artificial corona made of human plasma proteins drastically reduces capture by circulating leukocytes in whole blood and may be an effective strategy to enable prolonged circulation in vivo. We conclude with a critical assessment of the key concepts of liposome technology that need to be reviewed for its definitive clinical translation.