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

Protein-resistant, reductively dissociable polyplexes for in vivo systemic delivery and tumor-targeting of siRNA. Biomaterials. 2013 Mar;34(9):2370-9 Authors: Kim JS, Oh MH, Park JY, Park TG, Nam YS Abstract 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. PMID: 23294546 [PubMed - in process]
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research