title: Efficient siRNA delivery using a polyamidoamine dendrimer with a modified pentaerythritol core.
abstract: OBJECTIVE
  Delivery of siRNA into cells remains a critical challenge. Our lab has shown a novel polyamidoamine (PAMAM) dendrimer with modified pentaerythritol derivative core (PD dendrimer) to exhibit high plasmid DNA transfection efficiency and low cytotoxicity. Here, we evaluate PD dendrimer as a siRNA carrier.
  
  
  METHODS
  Agarose gel electrophoresis and AFM were used to confirm formation of generation 5 (G5)-PD dendrimer/siRNA nanoparticles (NPs). G5 PD dendrimer/anti-luciferase siRNA NPs were used to transfect SK Hep-1 cells with stable luciferase expression. Effects of various endocytic pathway inhibitors on uptake of G5 PD dendrimer/siRNA NPs in SK Hep-1 cells were also investigated.
  
  
  RESULTS
  Agarose gel electrophoresis indicated that G5 PD dendrimer and siRNA formed NPs at weight ratios >0.5:1. G5 PD dendrimer showed effective luciferase gene silencing when weight ratio was 3.0:1 and above. Treatment with endocytosis inhibitors showed that clathrin-mediated endocytosis was the main endocytic pathway by which G5-PD dendrimer/siRNA NPs enter the cell.
  
  
  CONCLUSIONS
  These results show that the novel G5 PD dendrimer has high siRNA delivery activity and is promising as a delivery agent for its therapeutic application.
authors.affiliation: College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, Nankai University Tianjin 300071, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices (NSEC-CANPBD) The Ohio State University Columbus, Ohio 43210, USA.
authors.forename: Chenguang
authors.initials: C
authors.lastname: Zhou
authors.affiliation: NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices (NSEC-CANPBD) The Ohio State University Columbus, Ohio 43210, USA.
authors.forename: Kwang Joo
authors.initials: KJ
authors.lastname: Kwak
authors.affiliation: NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices (NSEC-CANPBD) The Ohio State University Columbus, Ohio 43210, USA.
authors.forename: Xinmei
authors.initials: X
authors.lastname: Wang
authors.affiliation: NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices (NSEC-CANPBD) The Ohio State University Columbus, Ohio 43210, USA.
authors.forename: Bryant
authors.initials: B
authors.lastname: Yung
authors.affiliation: NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices (NSEC-CANPBD) The Ohio State University Columbus, Ohio 43210, USA.
authors.forename: L James
authors.initials: LJ
authors.lastname: Lee
authors.affiliation: College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, Nankai University Tianjin 300071, China.
authors.forename: Yanming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, Nankai University Tianjin 300071, China.
authors.forename: Peng George
authors.initials: PG
authors.lastname: Wang
authors.affiliation: NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices (NSEC-CANPBD) The Ohio State University Columbus, Ohio 43210, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lee
mesh_terms: D045744:Cell Line, Tumor; D002966:Clathrin / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D050091:Dendrimers / Q000737:chemistry* / Q000633:toxicity; D004587:Electrophoresis, Agar Gel; D004705:Endocytosis / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism; D018625:Microscopy, Atomic Force; D053758:Nanoparticles; D011409:Propylene Glycols / Q000737:chemistry* / Q000633:toxicity; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000737:chemistry / Q000378:metabolism*; D013395:Sucrose / Q000494:pharmacology; D014162:Transfection / Q000379:methods*
chemical_list: D002966:Clathrin; D050091:Dendrimers; D011409:Propylene Glycols; D034741:RNA, Small Interfering; D015638:Cytochalasin D; D013395:Sucrose; D008156:Luciferases; C008783:pentaerythritol