Protein-resistant, reductively dissociable polyplexes for in vivo systemic delivery and tumor-targeting of siRNA

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Small interfering RNA (siRNA) has been considered as a very attractive therapeutic alternative to chemical drugs; however, the chemical and biological instability and poor delivery efficiency of siRNA limit its success in clinical applications. Here we report a protein-resistant, reductively dissociable siRNA delivery system based on self-assembled polyelectrolyte complexes of dextran-siRNA conjugates linked by disulfide bonds. The prepared polyplexes exhibit excellent dispersion stability in the presence of serum because of the anti-fouling property of dextran exposed onto the complex surface. The enzymatic degradation of siRNA is also effectively suppressed within the complex. Folates are introduced as an active tumor-targeting moiety via the conjugation of folates to the hydroxyl groups of dextran. An in vivo investigation with a xenograft tumor mouse model shows that the folate-decorated dextran-siRNA conjugates are very efficiently targeted to cancer cells and induce sequence-specific gene silencing. (C) 2012 Elsevier Ltd. All rights reserved.
Publisher
ELSEVIER SCI LTD
Issue Date
2013-03
Language
English
Article Type
Article
Keywords

GENE-THERAPY; RNA INTERFERENCE; DEXTRAN; THERAPEUTICS; CONJUGATE; ACID; NANOPARTICLES; MOLECULES; PROSPECTS; ARGININE

Citation

BIOMATERIALS, v.34, no.9, pp.2370 - 2379

ISSN
0142-9612
DOI
10.1016/j.biomaterials.2012.12.004
URI
http://hdl.handle.net/10203/174521
Appears in Collection
BS-Journal Papers(저널논문)MS-Journal Papers(저널논문)
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