title: A nanoparticle system specifically designed to deliver short interfering RNA inhibits tumor growth in vivo.
abstract: Use of short interfering RNA (siRNA) is a promising new approach thought to have a strong potential to lead to rapid development of gene-oriented therapies. Here, we describe a newly developed, systemically injectable siRNA vehicle, the "wrapsome" (WS), which contains siRNA and a cationic lipofection complex in a core that is fully enveloped by a neutral lipid bilayer and hydrophilic polymers. WS protected siRNA from enzymatic digestion, providing a long half-life in the systemic circulation. Moreover, siRNA/WS leaked from blood vessels within tumors into the tumor tissue, where it accumulated and was subsequently transfected into the tumor cells. Because the transcription factor KLF5 is known to play a role in tumor angiogenesis, we designed KLF5-siRNA to test the antitumor activity of siRNA/WS. KLF5-siRNA/WS exhibited significant antitumor activity, although neither WS containing control scrambled-siRNA nor saline containing KLF5-siRNA affected tumor growth. KLF5-siRNA/WS inhibited Klf5 expression within tumors at both mRNA and protein levels, significantly reducing angiogenesis, and we detected no significant acute or long-term toxicity. Our findings support the idea that siRNA/WS can be used to knock down specific genes within tumors and thereby exert therapeutic effects against cancers.
authors: Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Japan.
authors: Nobuhiro
authors: N
authors: Yagi
authors: Ichiro
authors: I
authors: Manabe
authors: Tsuneaki
authors: T
authors: Tottori
authors: Atsushi
authors: A
authors: Ishihara
authors: Fusa
authors: F
authors: Ogata
authors: Jong Heon
authors: JH
authors: Kim
authors: Satoshi
authors: S
authors: Nishimura
authors: Katsuhito
authors: K
authors: Fujiu
authors: Yumiko
authors: Y
authors: Oishi
authors: Keiji
authors: K
authors: Itaka
authors: Yasuki
authors: Y
authors: Kato
authors: Masahiro
authors: M
authors: Yamauchi
authors: Ryozo
authors: R
authors: Nagai
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects*; D016503:Drug Delivery Systems / Q000379:methods*; D018014:Gene Transfer Techniques; D006207:Half-Life; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use*; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology*; D020871:RNA Stability; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D051598:Whole Body Imaging / Q000379:methods
chemical_list: D002232:Carbocyanines; C492214:KLF5 protein, human; D051741:Kruppel-Like Transcription Factors; D034741:RNA, Small Interfering; C085321:cyanine dye 5