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Self‐crosslinked and reducible fusogenic peptides for intracellular delivery of siRNA
Author(s) -
Mok Hyejung,
Park Tae Gwan
Publication year - 2008
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.21032
Subject(s) - polyethylenimine , chemistry , peptide , transfection , cytotoxicity , conjugate , polyelectrolyte , gene silencing , biophysics , small interfering rna , peg ratio , gene delivery , green fluorescent protein , intracellular , biochemistry , in vitro , gene , organic chemistry , polymer , biology , mathematical analysis , finance , economics , mathematics
Abstract A novel self‐crosslinked and reducible peptide was synthesized for stable formation of nanoscale complexes with an siRNA‐PEG conjugate to enhance transfection efficiency in serum containing condition without compromising cytotoxicity. A fusogenic peptide, KALA, with two cysteine residues at both terminal ends was crosslinked via disulfide linkages under mild DMSO oxidation condition. The reducible crosslinked KALA (cl‐KALA) was used to form nano‐complexes with green fluorescent protein (GFP) siRNA. Size and morphology of various polyelectrolyte complexes formulated with KALA and cl‐KALA were comparatively analyzed. cl‐KALA exhibited more reduced cell cytotoxicity and formed more stable and compact polyelectrolyte complexes with siRNA, compared with naked KALA and polyethylenimine (PEI), probably because of its increased charge density. The extent of gene silencing was quantitatively evaluated using MDA‐MB‐435 cells. cl‐KALA/siRNA complexes showed comparable gene silencing efficiency with those of cytotoxic PEI. In a serum containing medium, cl‐KALA/siRNA‐PEG conjugate complexes exhibited superior gene inhibition because of the shielding effect of PEG on the surface. The formulation based on the self‐crosslinked fusogenic peptide could be used as a biocompatible and efficient nonviral carrier for siRNA delivery. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 881–888, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com