| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2083503 | European Journal of Pharmaceutics and Biopharmaceutics | 2014 | 6 Pages |
•Downregulation of Syn-4 improves internalization of PEG-PAMAM based DNA polyplexes in HepG2 cells.•Downregulation of Syn-4 decreases internalization of PEG-PAMAM based DNA polyplexes in C2C12 cells.•Upregulation of CAV-1 improves internalization of PEG-PAMAM based DNA polyplexes in HepG2 cells.•CAV-1 does not involve in the internalization of PEG-PAMAM based DNA polyplexes in C2C12 cells.
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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