Polyion complex stability and gene silencing efficiency with a siRNA-grafted polymer delivery system.
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.
Takemoto
Hiroyasu
H
Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan.
Ishii
Atsushi
A
Miyata
Kanjiro
K
Nakanishi
Masataka
M
Oba
Makoto
M
Ishii
Takehiko
T
Yamasaki
Yuichi
Y
Nishiyama
Nobuhiro
N
Kataoka
Kazunori
K
D000818:Animals; D001218:Aspartame / Q000737:chemistry; D016923:Cell Death; D045744:Cell Line, Tumor; D004058:Diffusion; D004587:Electrophoresis, Agar Gel; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D020868:Gene Silencing; D018014:Gene Transfer Techniques; D016898:Interferon-alpha / Q000096:biosynthesis; D042541:Intracellular Space / Q000378:metabolism; D007477:Ions / Q000737:chemistry*; D051379:Mice; D018613:Microscopy, Confocal; D011108:Polymers / Q000737:chemistry*; D034741:RNA, Small Interfering / Q000378:metabolism*
D016898:Interferon-alpha; D007477:Ions; D011108:Polymers; D034741:RNA, Small Interfering; D001218:Aspartame