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.