Efficient siRNA Delivery Using PEG-conjugated PAMAM Dendrimers Targeting Vascular Endothelial Growth Factor in a CoCl2-induced Neovascularization Model in Retinal Endothelial Cells

Author(s): Lu Xu , Wenwen Shen , Bin Wang , Xinlei Wang , George Liu , Yong Tao , Rong Qi .

Journal Name: Current Drug Delivery

Volume 13 , Issue 4 , 2016

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Abstract:

Background: Choroidal neovascularization (CNV), also known as subretinal neovascularization, causes serious damage to the central vision as it happens more commonly in macula. The most important factor involved in angiogenesis is vascular endothelial growth factor (VEGF). By an RNAi technique, VEGF gene knockdown can be used to treat CNV. PEG-conjugated poly (amidoamine) (PEGPAMAM) dendrimers as a new type of synthetic polymers are very promising to be gene delivery carriers.

Methods: To investigate siRNA delivery efficacy of PEG-PAMAM dendrimers, we prepared dendriplexes of PEG-PAMAM dendrimers with a fluorescence-labelled siRNA (PEG-PAMAM/FAM siRNA) or VEGF siRNA (PEG-PAMAM/VEGF siRNA), and studied transfection and downregulation efficacy of the dendriplexes in a cobalt chloride (CoCl2)-induced neovascularization model in retinal vascular endothelial cells (RF/6A).

Results: Our results demonstrate that PEG-PAMAM dendrimers had significantly higher transfection efficiency to FAM siRNA than a commercial transfection reagent PEI (1.4-fold, P<0.001) measured by flow cytometry. Compared to the PEI/VEGF siRNA polyplexes, the dendriplexes of the PEG-PAMAM/VEGF siRNA more significantly downregulated VEGF gene expression (P < 0.01) at both mRNA and protein expression level. A tube formation assay also proved that the PEG-PAMAM/VEGF siRNA dendriplexes more significantly inhibited vascular-like formation than PEI/VEGF siRNA did (P < 0.001) in RF/6A.

Conclusion: This study demonstrated that G5-PEG was more efficient than PEI in facilitating siRNA delivery, downregulating VEGF expression and inhibiting vascular-like formation on RF/6A.

Keywords: Choroidal neovascularization, gene silencing efficacy, PEG-conjugated PAMAM dendrimers, retinal vascular endothelial cells, siRNA, vascular endothelial growth factor.

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Article Details

VOLUME: 13
ISSUE: 4
Year: 2016
Page: [590 - 599]
Pages: 10
DOI: 10.2174/1567201812666150817123049
Price: $58

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