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- W2611271882 abstract "A α-helical GALA peptide (WEAALAEALAEALAEHLAEALAEALEALAA) has been found to possess dual functions: a pH-dependent inducer of endosomal escape, and a ligand that targets lung endothelium. In the present study, the flexibility of GALA was improved by modifying the edge with polyethylene glycol linker, to increase lung-targeting activity. We first investigated the uptake of the GALA-modified liposomes in which GALA was directly conjugated to the lipid (Cholesterol: GALA/Chol) or the phospholipid-PEG (GALA/PEG2000). The liposomes that were modified with GALA/PEG2000 (GALA/PEG2000-LPs) were taken up at a higher level by human lung endothelial cells (HMVEC-L), in comparison with particles that were modified with GALA/Chol (GALA/Chol-LPs). Small-interfering RNA–encapsulating liposomal-based nanocarriers (multifunctional envelope-type nano device: MEND) that were formulated with a vitamin E-scaffold SS-cleavable pH-activated lipid-like material, namely GALA/PEG2000-MENDssPalmE were also modified with GALA/PEG2000. Gene silencing activity in the lung endothelium was then evaluated against an endothelial marker; CD31. In comparison with the unmodified MENDssPalmE, GALA/PEG2000-MENDssPalmE exhibited a higher silencing activity in the lung. Optimization of GALA/PEG2000-MENDssPalmE resulted in silencing activity in the lung with an ED50 value of 0.21 mg/kg, while non-specific gene silencing in liver was marginal. Collectively, PEGylated GALA is a promising device for use in targeting the lung endothelium." @default.
- W2611271882 created "2017-05-12" @default.
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- W2611271882 date "2017-09-01" @default.
- W2611271882 modified "2023-10-16" @default.
- W2611271882 title "PEGylation of the GALA Peptide Enhances the Lung-Targeting Activity of Nanocarriers That Contain Encapsulated siRNA" @default.
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- W2611271882 doi "https://doi.org/10.1016/j.xphs.2017.04.075" @default.
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