Document Detail


Efficient siRNA Delivery Using a Polyamidoamine Dendrimer with a Modified Pentaerythritol Core.
MedLine Citation:
PMID:  22274556     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
PURPOSE: 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:
Yue Zhang; Chenguang Zhou; Kwang Joo Kwak; Xinmei Wang; Bryant Yung; L James Lee; Yanming Wang; Peng George Wang; Robert J Lee
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-25
Journal Detail:
Title:  Pharmaceutical research     Volume:  -     ISSN:  1573-904X     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8406521     Medline TA:  Pharm Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China.
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