シアル酸修飾による糖蛋白質結合リポソームの細網内皮系（ＲＥＳ）への取り込み抑制と促進に関する検討

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  • Reduction and increase of the reticuloendotherial system(RES) uptake of glycoprotein-conjugated liposomes by linking a ternimal sugar-chain with sialic acid.

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Different sialic acid-linked glycoprotein-conjuagted liposomes were prepared. N-acetyl-glacosaminylated (GlcNAc) human albumin (HSA)-coupled iposomes (GlcNAc-HSA-Lip) were enzymatically galactosylated at 4-position, and fucosylated at 3-position of GlcNAc to prepare LX. Galactose of LX was enzymatically sialylated at 3-position to do SLX. GlcNAc of GlcNAc-HSA-Lip was modified with 3'-sialyated galactose, or 6'-sialyated galactose at 4-position, to prepare 3 SLN and 6 SLN, respectively. The reticuloendotherial system (RES) uptake of these conjugates was investigated in Ehrlich-solid tumor-bearing mice. Sialic acid linked with a terminal sugar chain of SLX increased the uptake by RES, such as liver and spleen. Whereas, sialic acid of 3 SLN and 6 SLN reduced the RES uptake. Besides, uptake of liposomes by tumor tissues was closely correlated with a long blood circulating character of these conjugates. These results suggest that sialic acid residue increases the RES uptake of glycoprotein-conjugated liposomes in presence of fucose-residue nearby, while it reduces the uptake via masking galactose-residue in absence of fucose-residue. Thus, modification of glycoprotein-conjugated liposomes with sialic acid may lead to be development of a useful carrier for drug delivery system (DDS).

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