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  • Title: Cytosolic targeting of macromolecules using a pH-dependent fusogenic peptide in combination with cationic liposomes.
    Author: Kobayashi S, Nakase I, Kawabata N, Yu HH, Pujals S, Imanishi M, Giralt E, Futaki S.
    Journal: Bioconjug Chem; 2009 May 20; 20(5):953-9. PubMed ID: 19388672.
    Abstract:
    pH-Sensitive peptides and polymers have been employed as additives to enhance the cytosolic delivery of drugs and genes by facilitating their endosomal escape. However, little attention has been paid to the intracellular fate of these peptides and polymers. In this study, we explored the possibility of utilizing GALA, a pH-sensitive fusogenic peptide, as a cytosol-targeting vehicle. In combination with cationic liposomes, Lipofectamine 2000 (LF2000), the feasibility of this approach for the cytosolic targeting of proteins and nanoparticles was exemplified through the delivery of avidin (68 kDa) and streptavidin-coated quantum dots (15-20 nm) in serum-containing medium. The use of cationic liposomes is critical to enhance the cell-surface adhesion of the GALA conjugates and eventual endosomal uptake. Circular dichroism studies suggest that the GALA can be liberated from cationic liposomes at a reducing pH to form a helical structure and this may eventually lead to disruption of the endosomal membrane to achieve an efficient leakage of the GALA conjugates into the cytosol.
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