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Issue 2, 2018
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Hepatocellular targeted α-tocopherol based pH sensitive galactosylated lipids: design, synthesis and transfection studies

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Abstract

Receptor mediated gene delivery to the liver offers advantages in treating genetic disorders such as hemophilia and hereditary tyrosinemia type I (HTI). Prior findings demonstrated that tethering the D-galactose head group to cationic lipids directs genes to the liver via asialoglycoprotein receptors (ASGPRs). In our continued efforts to develop safer and efficient lipofectins, we demonstrated that cationic lipids bearing α-tocopherol, an antioxidant, as a hydrophobic domain could deliver genes efficiently with high safety profiles in multiple cell lines. Towards developing ASGPR targeted pH sensitive cationic lipids, we have designed a galactosylated cationic lipid (Toc-Gal) with α-tocopherol as the hydrophobic core covalently connected with a pH responsive triazole moiety and a non-targeting control lipid (Toc-OH) without the galactose head group. In this study, we present the design and synthesis of a pH sensitive galactosylated cationic lipid (Toc-Gal), its comparative transfection biology, cellular uptake studies, serum stability and cytotoxicity profiles in both ASGPR positive and negative liver cells, i.e. HepG2 and SK-Hep-1, respectively.

Graphical abstract: Hepatocellular targeted α-tocopherol based pH sensitive galactosylated lipids: design, synthesis and transfection studies

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Publication details

The article was received on 08 Oct 2017, accepted on 05 Dec 2017 and first published on 06 Dec 2017


Article type: Research Article
DOI: 10.1039/C7MD00503B
Citation: Med. Chem. Commun., 2018,9, 264-274
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    Hepatocellular targeted α-tocopherol based pH sensitive galactosylated lipids: design, synthesis and transfection studies

    V. Muripiti, B. Lohchania, S. K. Marepally and S. V. Patri, Med. Chem. Commun., 2018, 9, 264
    DOI: 10.1039/C7MD00503B

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