Journal
PHARMACEUTICAL RESEARCH
Volume 29, Issue 6, Pages 1627-1636Publisher
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s11095-012-0676-x
Keywords
endocytosis; gene silencing; PAMAM dendrimer; siRNA delivery
Funding
- Natural Science Foundation of China [50803029]
- NIH [R01CA135243]
- NSF [EEC-0425626]
- Div Of Engineering Education and Centers
- Directorate For Engineering [914790] Funding Source: National Science Foundation
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Delivery of siRNA into cells remains a critical challenge. Our lab has shown a novel polyamidoamine (PAMAM) dendrimer with modified pentaerythritol derivative core (PD dendrimer) to exhibit high plasmid DNA transfection efficiency and low cytotoxicity. Here, we evaluate PD dendrimer as a siRNA carrier. Agarose gel electrophoresis and AFM were used to confirm formation of generation 5 (G5)-PD dendrimer/siRNA nanoparticles (NPs). G5 PD dendrimer/anti-luciferase siRNA NPs were used to transfect SK Hep-1 cells with stable luciferase expression. Effects of various endocytic pathway inhibitors on uptake of G5 PD dendrimer/siRNA NPs in SK Hep-1 cells were also investigated. Agarose gel electrophoresis indicated that G5 PD dendrimer and siRNA formed NPs at weight ratios > 0.5:1. G5 PD dendrimer showed effective luciferase gene silencing when weight ratio was 3.0:1 and above. Treatment with endocytosis inhibitors showed that clathrin-mediated endocytosis was the main endocytic pathway by which G5-PD dendrimer/siRNA NPs enter the cell. These results show that the novel G5 PD dendrimer has high siRNA delivery activity and is promising as a delivery agent for its therapeutic application.
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