title: Long dsRNA-mediated RNA interference and immunostimulation: a targeted delivery approach using polyethyleneimine based nano-carriers.
abstract: RNA oligonucleotides capable of inducing controlled immunostimulation combined with specific oncogene silencing via an RNA interference (RNAi) mechanism provide synergistic inhibition of cancer cell growth. With this concept, we previously designed a potent immunostimulatory long double stranded RNA, referred to as liRNA, capable of executing RNAi mediated specific target gene silencing. In this study, we developed a highly effective liRNA based targeted delivery system to apply in the treatment of glioblastoma multiforme. A stable nanocomplex was fabricated by complexing multimerized liRNA structures with cross-linked branched poly(ethylene imine) (bPEI) via electrostatic interactions. We show clear evidence that the cross-linked bPEI was quite effective in enhancing the cellular uptake of liRNA on U87MG cells. Moreover, the liRNA-PEI nanocomplex provided strong RNAi mediated target gene silencing compared to that of the conventional siRNA-PEI complex. Further, the bPEI modification strategy with specific ligand attachment assisted the uptake of the liRNA-PEI complex on the mouse brain endothelial cell line (b.End3). Such delivery systems combining the beneficial elements of targeted delivery, controlled immunostimulation, and RNAi mediated target silencing have immense potential in anticancer therapy.
authors: Global Research Laboratory for RNAi Medicine, Department of Chemistry, Sungkyunkwan University , Suwon 440-746, Republic of Korea.
authors: S
authors: S
authors: Sajeesh
authors: Tae Yeon
authors: TY
authors: Lee
authors: Sun Woo
authors: SW
authors: Hong
authors: Pooja
authors: P
authors: Dua
authors: Jeong Yong
authors: JY
authors: Choe
authors: Aeyeon
authors: A
authors: Kang
authors: Wan Soo
authors: WS
authors: Yun
authors: Changsik
authors: C
authors: Song
authors: Sung Ha
authors: SH
authors: Park
authors: Soyoun
authors: S
authors: Kim
authors: Chiang
authors: C
authors: Li
authors: Dong-Ki
authors: DK
authors: Lee
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004337:Drug Carriers; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D018014:Gene Transfer Techniques; D005909:Glioblastoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018625:Microscopy, Atomic Force; D011094:Polyethyleneimine / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D004337:Drug Carriers; D051034:Inhibitor of Apoptosis Proteins; D011108:Polymers; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D000077022:Survivin; D011094:Polyethyleneimine
keywords: RNA interference; glioblastoma; immunostimulation; nanotechnology; siRNA delivery; targeted delivery