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Efficient siRNA Delivery Using a Polyamidoamine Dendrimer with a Modified Pentaerythritol Core

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Abstract

Purpose

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.

Methods

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.

Results

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.

Conclusions

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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ACKNOWLEDGMENTS & DISCLOSURES

This research was supported by Natural Science Foundation of China (No. 50803029), NIH grant R01CA135243, and NSF grant EEC-0425626 to R. Lee.

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Authors and Affiliations

  1. College of Pharmacy, State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China

    Yue Zhang, Yanming Wang & Peng George Wang

  2. NSF Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices (NSEC-CANPBD), The Ohio State University, Columbus, Ohio, 43210, USA

    Chenguang Zhou, Kwang Joo Kwak, Xinmei Wang, Bryant Yung, L. James Lee & Robert J. Lee

  3. Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, Ohio, 43210, USA

    L. James Lee

  4. Department of Chemistry, Georgia State University, Atlanta, Georgia, 30302, USA

    Peng George Wang

  5. Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, Ohio, 43210, USA

    Yue Zhang, Chenguang Zhou, Bryant Yung & Robert J. Lee

Authors
  1. Yue Zhang
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  2. Chenguang Zhou
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  3. Kwang Joo Kwak
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  4. Xinmei Wang
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  5. Bryant Yung
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  6. L. James Lee
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  7. Yanming Wang
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  8. Peng George Wang
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  9. Robert J. Lee
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Corresponding authors

Correspondence to Yanming Wang, Peng George Wang or Robert J. Lee.

Additional information

Yue Zhang and Chenguang Zhou contributed equally to this work.

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Zhang, Y., Zhou, C., Kwak, K.J. et al. Efficient siRNA Delivery Using a Polyamidoamine Dendrimer with a Modified Pentaerythritol Core. Pharm Res 29, 1627–1636 (2012). https://doi.org/10.1007/s11095-012-0676-x

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  • DOI: https://doi.org/10.1007/s11095-012-0676-x

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