title: Novel PEI/Poly-γ-Gutamic Acid Nanoparticles for High Efficient siRNA and Plasmid DNA Co-Delivery.
abstract: The efficient delivery of sufficient amounts of nucleic acids into target cells is critical for successful gene therapy and gene knockdown. The DNA/siRNA co-delivery system has been considered a promising approach for cancer therapy to simultaneously express and inhibit tumor suppressor genes and overexpressed oncogenes, respectively, triggering synergistic anti-cancer effects. Polyethylenimine (PEI) has been identified as an efficient non-viral vector for transgene expression. In this study, we created a very high efficient DNA/siRNA co-delivery system by incorporating a negatively-charged poly-γ-glutamic acid (γ-PGA) into PEI/nucleic acid complexes. Spherical nanoparticles with about 200 nm diameter were formed by mixing PEI/plasmid DNA/siRNA/γ-PGA (dual delivery nanoparticles; DDNPs) with specific ratio (N/P/C ratio) and the particles present positive surface charge under all manufacturing conditions. The gel retardation assay shows both nucleic acids were effectively condensed by PEI, even at low N/P ratios. The PEI-based DDNPs reveal excellent DNA/siRNA transfection efficiency in the human hepatoma cell line (Hep 3B) by simultaneously providing high transgene expression efficiency and high siRNA silencing effect. The results indicated that DDNP can be an effective tool for gene therapy against hepatoma.
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan. sfpeng@mail.cmu.edu.tw.|Department of Medical Research, China Medical University Hospital, Taichung 40402, Taiwan. sfpeng@mail.cmu.edu.tw.
authors.forename: Shu-Fen
authors.initials: SF
authors.lastname: Peng
authors.affiliation: Institute of Bioinformatics and Structural Biology, National Tsing-Hua University, Hsinchu 30013, Taiwan. d947624@gmail.com.
authors.forename: Hung-Kun
authors.initials: HK
authors.lastname: Hsu
authors.affiliation: Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan. cclin66@mx.nthu.edu.tw.
authors.forename: Chun-Cheng
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Department of Agronomy, National Chung Hsing University, Taichung 40402, Taiwan. ymcheng@dragon.nchu.edu.tw.
authors.forename: Ya-Ming
authors.initials: YM
authors.lastname: Cheng
authors.affiliation: Department of Biological Science and Technology, China Medical University, Taichung 40402, Taiwan. s5439003@hotmail.com.
authors.forename: Kuang-Hsing
authors.initials: KH
authors.lastname: Hsu
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D015870:Gene Expression; D020868:Gene Silencing; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism*; D011094:Polyethyleneimine / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014162:Transfection / Q000379:methods*
chemical_list: D008164:Luminescent Proteins; D034741:RNA, Small Interfering; C413663:fluorescent protein 583; C511775:poly(gamma-glutamic acid); D049452:Green Fluorescent Proteins; D011099:Polyglutamic Acid; D011094:Polyethyleneimine
keywords: dual delivery nanoparticle; gene delivery; poly-γ-glutamic acid; polyethylenimine; siRNA delivery