Journal
BIOMATERIALS
Volume 34, Issue 9, Pages 2370-2379Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.12.004
Keywords
siRNA; Dextran; Polyethylenimine; Biodegradation; Nanoparticle; Folate
Funding
- Korean Health 21 R&D Project of the Ministry of Health & Welfare, Republic of Korea [A040041]
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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.
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