title: The role of caveolin-1 and syndecan-4 in the internalization of PEGylated PAMAM dendrimer polyplexes into myoblast and hepatic cells.
abstract: To improve gene delivery efficiency of PEGylated poly(amidoamine) dendrimers in livers and muscles, the roles of syndecan-4 receptor and caveolin-1 protein in the endocytosis of PEGylated generation 5 (G5-PEG) or 7 (G7-PEG) dendrimers and plasmid DNA polyplexes were explored in C2C12 and HepG2 cells. Expression levels of syndecan-4 for both cell lines were downregulated by transfection of the cells with syndecan-4 specific siRNA. Caveolin-1 was upregulated by infecting the cells with adenovirus vector expressed caveolin-1 (Ad-CAV-1). The impact of syndecan-4 and caveolin-1 on endocytosis of G5-PEG/DNA or G7-PEG/DNA polyplexes was then measured by flow cytometry. Our results demonstrate that downregulation of syndecan-4 and upregulation of caveolin-1 significantly improved internalization of PEG-PAMAM dendrimer polyplexes in HepG2 cells; however, in C2C12 cells, downregulation of syndecan-4 decreased the internalization of the polyplexes while upregulation of caveolin-1 had no effect on internalization. Gene expression results for G5-PEG/pGFP on the two cell lines exhibited the same trends for syndecan-4 and caveolin-1 as was observed for endocytosis of the polyplexes. This study gives a clue how to take strategies by up- or down-regulation of the expressions of syndecan-4 and caveolin-1 to improve in vivo gene delivery efficiency of the PEG-PAMAM dendrimers in clinical transgenic therapy.
authors.affiliation: Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Shen
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Mallory A
authors.initials: MA
authors.lastname: van Dongen
authors.affiliation: Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China.
authors.forename: Yingchun
authors.initials: Y
authors.lastname: Han
authors.affiliation: Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China.
authors.forename: Maomao
authors.initials: M
authors.lastname: Yu
authors.affiliation: Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China.
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China.
authors.forename: George
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Banaszak Holl
authors.affiliation: Peking University Institute of Cardiovascular Sciences, Peking University Health Science Center, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, China. Electronic address: ronaqi@bjmu.edu.cn.
authors.forename: Rong
authors.initials: R
authors.lastname: Qi
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000235:genetics*; D002470:Cell Survival; D004247:DNA / Q000008:administration & dosage / Q000235:genetics; D050091:Dendrimers / Q000737:chemistry* / Q000633:toxicity; D015536:Down-Regulation; D004337:Drug Carriers / Q000737:chemistry* / Q000633:toxicity; D004705:Endocytosis; D015870:Gene Expression; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000378:metabolism*; D051379:Mice; D032446:Myoblasts / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000633:toxicity; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D053671:Syndecan-4 / Q000235:genetics*; D014162:Transfection; D015854:Up-Regulation
chemical_list: D051242:Caveolin 1; D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D034741:RNA, Small Interfering; D053671:Syndecan-4; D011092:Polyethylene Glycols; D004247:DNA
keywords: C2C12; Caveolin-1; Endocytosis mechanism; HepG2; PAMAM dendrimer (Pubchem CID:4140276); PEG-PAMAM dendrimer polyplex; Polyethylene glycol (Pubchem CID:174); Syndecan-4
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