Polyion complex stability and gene silencing efficiency with a siRNA-grafted polymer delivery system

Abstract An siRNA-grafted polymer through disulfide linkage was prepared to improve the physicochemical properties and transfection efficacies of the polyion complexes (PICs) as a nanocarrier of siRNA. The siRNA-grafted polymer formed stable PICs due to its larger numbers and higher density of anion...

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Bibliographic Details
Published in:Biomaterials 2010-11, Vol.31 (31), p.8097-8105
Main Authors: Takemoto, Hiroyasu, Ishii, Atsushi, Miyata, Kanjiro, Nakanishi, Masataka, Oba, Makoto, Ishii, Takehiko, Yamasaki, Yuichi, Nishiyama, Nobuhiro, Kataoka, Kazunori
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Aspartame - chemistry
Cell Death
Cell Line, Tumor
Dentistry
Diffusion
Electrophoresis, Agar Gel
Electrophoresis, Polyacrylamide Gel
Endosome escape
Flow Cytometry
Gene Silencing
Gene Transfer Techniques
Graft copolymer
Interferon-alpha - biosynthesis
Intracellular Space - metabolism
Ions - chemistry
Mice
Microscopy, Confocal
Poly(aspartate)
Polyion complex
Polymers - chemistry
RNA, Small Interfering - metabolism
siRNA
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Summary:Abstract An siRNA-grafted polymer through disulfide linkage was prepared to improve the physicochemical properties and transfection efficacies of the polyion complexes (PICs) as a nanocarrier of siRNA. The siRNA-grafted polymer formed stable PICs due to its larger numbers and higher density of anionic charges compared with monomeric siRNA, leading to effective internalization by cultured cells. Following the endosomal escape of the PIC, the disulfide linkage of the siRNA-grafted polymer allowed efficient siRNA release from the PIC under intracellular reductive conditions. Consequently, the PIC from the siRNA-grafted polymer showed a potent gene silencing effect without cytotoxicity or immunogenicity, demonstrating a promising feature of the siRNA-grafted polymer to construct the PIC-based nanocarrier for in vivo siRNA delivery.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2010.07.015