The role of caveolin-1 and syndecan-4 in the internalization of PEGylated PAMAM dendrimer polyplexes into myoblast and hepatic cells

Wenwen Shen, Mallory A. van Dongen, Yingchun Han, Maomao Yu, Yanzhi Li, George Liu, Mark M. Banaszak Holl, Rong Qi

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)658-663
Number of pages6
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume88
Issue number3
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

Keywords

  • C2C12
  • Caveolin-1
  • Endocytosis mechanism
  • HepG2
  • PEG-PAMAM dendrimer polyplex
  • Syndecan-4

Cite this

Shen, Wenwen ; van Dongen, Mallory A. ; Han, Yingchun ; Yu, Maomao ; Li, Yanzhi ; Liu, George ; Banaszak Holl, Mark M. ; Qi, Rong. / The role of caveolin-1 and syndecan-4 in the internalization of PEGylated PAMAM dendrimer polyplexes into myoblast and hepatic cells. In: European Journal of Pharmaceutics and Biopharmaceutics. 2014 ; Vol. 88, No. 3. pp. 658-663.
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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.",
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The role of caveolin-1 and syndecan-4 in the internalization of PEGylated PAMAM dendrimer polyplexes into myoblast and hepatic cells. / Shen, Wenwen; van Dongen, Mallory A.; Han, Yingchun; Yu, Maomao; Li, Yanzhi; Liu, George; Banaszak Holl, Mark M.; Qi, Rong.

In: European Journal of Pharmaceutics and Biopharmaceutics, Vol. 88, No. 3, 01.01.2014, p. 658-663.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Yu, Maomao

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