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LIPID-MODIFIED INSULIN INCORPORATED LIPOSOMES FOR SELECTIVELY DELIVERING CYTOTOXIC AGENTS TO HEPATOMA CELLS
LIPID-MODIFIED INSULIN INCORPORATED LIPOSOMES FOR SELECTIVELY DELIVERING CYTOTOXIC AGENTS TO HEPATOMA CELLS
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机译:脂质修饰的胰岛素掺入的脂质体,选择性地将细胞毒性剂递送至肝细胞
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摘要
The present invention provides a lipid-modified insulin comprising an insulin molecule linked to an alkyl group by an amine linkage. Preferably, the alkyl group is a straight chain carbon comprising from about 14 to 20 carbon atoms. Preferably, the alkyl group is linked to the B1 phenylalanine or the B29 lysine. The present invention also provides a liposome comprising such lipid-modified insulin. Preferably, the liposomes are small unilamellar vesicles (SUVs) which have a particle size of less than 100 nm. The present invention also provides a method for making a lipid-modified insulin. The method comprises reacting the protein with a hydrophobic aldehyde in the presence of a reducing agent to provide a lipid-modified insulin in which an amino acid of the insulin is linked to an alkyl group by an amine linkage. The present invention also relates to a method of killing hepatoma cells, particularly the hepatoma cells that are found in a hepatocellular carcinoma. The method comprises the steps of: providing liposomes containing a cytotoxic agent and having a lipid-modified insulin associated with the lipid bilayer thereof and exposing the hepatoma cells to the liposomes.
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