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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Characteristics of the hepatic stellate cell-selective carrier mannose 6-phosphate modified albumin (M6P(28)-HSA).

BACKGROUND/AIMS: Drug targeting to hepatic stellate cells (HSC) may improve the pharmacological effects of antifibrotic drugs. Recently, albumin substituted with 28 mannose 6-phosphate moieties (M6P(28)-HSA) was found to distribute selectively to HSC in fibrotic rat livers. To assess whether this albumin can be used as a carrier for intracellular drug delivery, we explored the cellular handling of M6P(28)-HSA in HSC. METHODS/RESULTS: Application of competitive substrates for the M6P/IGFII receptor or other receptors showed that the binding of M6P-HSA to the M6P/IGFII receptor is specific. Binding was strong to activated HSC, but not to quiescent HSC. Furthermore, M6P(28)-HSA was extensively internalized by these cells. Using monensin, a specific inhibitor of the lysosomal pathway, proof was obtained that M6P-HSA is endocytosed via this route. The experiments performed with tissue slices, prepared from rat and human livers, revealed a specific binding and uptake of M6P(28)-HSA in both normal and cirrhotic livers. In livers from cirrhotic patients, HSC contributed predominantly to the uptake of this neoglycoprotein. CONCLUSIONS: Based on our in vivo data demonstrating the HSC-selectivity and on our in vitro data demonstrating binding and rapid internalization in activated HSC, we conclude that M6P(28)-HSA is applicable as a stellate cell-selective carrier for antifibrotic drugs that act intracellularly. This may have implications for the design of new strategies for the treatment of liver fibrosis.[1]


  1. Characteristics of the hepatic stellate cell-selective carrier mannose 6-phosphate modified albumin (M6P(28)-HSA). Beljaars, L., Olinga, P., Molema, G., de Bleser, P., Geerts, A., Groothuis, G.M., Meijer, D.K., Poelstra, K. Liver (2001) [Pubmed]
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