title: Low-Molecular-Weight Polyethyleneimine Grafted Polythiophene for Efficient siRNA Delivery.
abstract: Owing to its hydrophilicity, negative charge, small size, and labile degradation by endogenous nucleases, small interfering RNA (siRNA) delivery must be achieved by a carrier system. In this study, cationic copolymers composed of low-molecular-weight polyethylenimine and polythiophenes were synthesized and evaluated as novel self-tracking siRNA delivery vectors. The concept underlying the design of these copolymers is that hydrophobicity and rigidity of polythiophenes should enhance the transport of siRNA across the cell membrane and endosomal membrane. A gel retardation assay showed that the nanosized complexes formed between the copolymers and siRNA were stable even at a molar ratio of 1 : 2. The high cellular uptake (>80%) and localization of the copolymer vectors inside the cells were easily analyzed by tracking the fluorescence of polythiophene using fluorescent microscopy and cytometry. An in vitro luciferase knockdown (KD) assay in A549-luc cells demonstrated that the siRNA complexes with more hydrophobic copolymers achieved a higher KD efficiency of 52.8% without notable cytotoxicity, indicating protein-specific KD activity rather than solely the cytotoxicity of the materials. Our polythiophene copolymers should serve as novel, efficient, low cell toxicity, and label-free siRNA delivery systems.
authors.affiliation: Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Pan
authors.initials: P
authors.lastname: He
authors.affiliation: Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Hagiwara
authors.affiliation: Responsive Organic Materials Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Hui
authors.initials: H
authors.lastname: Chong
authors.affiliation: Responsive Organic Materials Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan ; Institute of Chemistry, Academia Sinica, 128 Academic Road, Section 2, Nankang, Taipei 11529, Taiwan.
authors.forename: Hsiao-hua
authors.initials: HH
authors.lastname: Yu
authors.affiliation: Nano Medical Engineering Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ito
mesh_terms: D002412:Cations / Q000008:administration & dosage / Q000737:chemistry; D002460:Cell Line; D024202:Electrophoretic Mobility Shift Assay; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D008970:Molecular Weight; D011094:Polyethyleneimine / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D013876:Thiophenes / Q000008:administration & dosage* / Q000737:chemistry; D014162:Transfection
chemical_list: D002412:Cations; D011108:Polymers; D034741:RNA, Small Interfering; D013876:Thiophenes; C066730:polythiophene; D011094:Polyethyleneimine