Binding patterns of peptide-containing liposomes in liver and spleen of developing mice: comparison with heparan sulfate immunoreactivity

Abstract

Liposomes incorporating peptide from the Plasmodium circumsporozoite protein (CSP) accumulate rapidly and selectively in adult mouse liver. The development of the liposome-binding pattern in liver and spleen was studied in relationship to the development of extracellular matrix molecules. Liposomes were administered to mice intravascularly or applied to the surface of liver and spleen slices in vitro. Slices were analyzed immunocytochemically. Liposomes were found along sinusoidal borders of liver, including the basolateral border of hepatocytes. The pattern was detected in the youngest animals studied (newborn). Intensity of heparan sulfate immunoreactivity increased until adult levels were reached at 20 days. Immunoreactivity for heparan sulfate proteoglycan, but not other proteoglycans, was detected in the youngest animals, and mimicked the pattern of liposome binding. The pattern of liposome binding in the spleen, concentrated in marginal zones, was similar to the pattern of heparan sulfate immunoreactivity, and also similar to the distribution of macrophage immunoreactivity. The postnatal development of liposome binding parallels the development of heparan sulfate immunoreactivity, supporting the suggestion that peptide-containing liposomes target liver by binding to heparan sulfate proteoglycans. Specific delivery of liposomes by targeting heparan sulfate proteoglycans is an effective strategy even at early time periods.