title: Protein-resistant, reductively dissociable polyplexes for in vivo systemic delivery and tumor-targeting of siRNA.
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.
authors.affiliation: Department of Materials Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Republic of Korea.
authors.forename: Jee Seon
authors.initials: JS
authors.lastname: Kim
authors.forename: Mi Hwa
authors.initials: MH
authors.lastname: Oh
authors.forename: Jae Yoon
authors.initials: JY
authors.lastname: Park
authors.forename: Tae Gwan
authors.initials: TG
authors.lastname: Park
authors.forename: Yoon Sung
authors.initials: YS
authors.lastname: Nam
mesh_terms: D000818:Animals; D002470:Cell Survival; D003911:Dextrans / Q000737:chemistry; D004195:Disease Models, Animal; D005260:Female; D005492:Folic Acid / Q000737:chemistry; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D006367:HeLa Cells; D006801:Humans; D007624:KB Cells; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry; D009369:Neoplasms / Q000235:genetics / Q000473:pathology; D011094:Polyethyleneimine / Q000737:chemistry; D011487:Protein Conformation; D034741:RNA, Small Interfering / Q000378:metabolism*; D014162:Transfection
chemical_list: D003911:Dextrans; D034741:RNA, Small Interfering; D011094:Polyethyleneimine; D005492:Folic Acid