Full Paper

PAMAM Dendrimers Mediate siRNA Delivery to Target Hsp27 and Produce Potent Antiproliferative Effects on Prostate Cancer Cells

  1. Xiao-xuan Liu1,2,
  2. Palma Rocchi Dr.3,
  3. Fan-qi Qu Prof.1,
  4. Shu-quan Zheng4,
  5. Zi-cai Liang Prof.5,
  6. Martin Gleave Prof.6,
  7. Juan Iovanna Dr.3,
  8. Ling Peng Dr.1,2

Article first published online: 16 JUN 2009

DOI: 10.1002/cmdc.200900076

Issue

ChemMedChem

ChemMedChem

Volume 4, Issue 8, pages 1302–1310, August 3, 2009

Additional Information

How to Cite

Liu, X.-x., Rocchi, P., Qu, F.-q., Zheng, S.-q., Liang, Z.-c., Gleave, M., Iovanna, J. and Peng, L. (2009), PAMAM Dendrimers Mediate siRNA Delivery to Target Hsp27 and Produce Potent Antiproliferative Effects on Prostate Cancer Cells. ChemMedChem, 4: 1302–1310. doi: 10.1002/cmdc.200900076

Author Information

  1. 1

    State Key Laboratory of Virology, College of Chemistry and Molecular Sciences, Wuhan University, Wuhan, 430072 (P. R. China), Fax: (+33) 4 91 82 93 01

  2. 2

    Centre Interdisciplinaire de Nanoscience de Marseille, CNRS UPR 3118, Département de Chimie, 163 avenue de Luminy, 13288 Marseille cedex 09 (France)

  3. 3

    NSERM, U624 “Stress Cellulaire”, 163 avenue de Luminy, 13288 Marseille cedex 09 (France)

  4. 4

    Suzhou Ribo Life Science, Zhongguancun Biomedical Garden, Beijing, 100085 (P. R. China)

  5. 5

    Institute of Molecular Medicine, Beijing University, Beijing (P. R. China)

  6. 6

    The Prostate Centre, Vancouver General Hospital, Vancouver, BC V6H 3Z6 (Canada)

Publication History

  1. Issue published online: 30 JUL 2009
  2. Article first published online: 16 JUN 2009
  3. Manuscript Revised: 18 MAY 2009
  4. Manuscript Received: 25 FEB 2009

Funded by

  • National Natural Science Foundation of China. Grant Numbers: 20572081, 20025311
  • CNRS
  • INSERM
  • Association Française contre les Myopathies. Grant Numbers: 13074, 10793
  • PPF CNP2. Grant Number: 20042462
  • COST Action. Grant Number: TD0802

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Keywords:

  • dendrimers;
  • gene delivery;
  • gene silencing;
  • Hsp27;
  • prostate cancer

Abstract

RNA interference (RNAi) holds great promise for the treatment of inherited and acquired diseases, provided that safe and efficient delivery systems are available. Herein we report that structurally flexible triethanolamine (TEA) core PAMAM dendrimers are able to deliver an Hsp27 siRNA effectively into prostate cancer (PC-3) cells by forming stable nanoparticles with siRNA, protecting the siRNA nanoparticles from enzymatic degradation, and enhancing cellular uptake of siRNA. The Hsp27 siRNA resulted in potent and specific gene silencing of heat-shock protein 27, an attractive therapeutic target in castrate-resistant prostate cancer. Silencing of the hsp27 gene led to induction of caspase-3/7-dependent apoptosis and inhibition of PC-3 cell growth in vitro. In addition, the siRNA–dendrimer complexes are non-cytotoxic under the conditions used for siRNA delivery. Altogether, TEA core PAMAM dendrimer-mediated siRNA delivery, in combination with RNAi that specifically targets Hsp27, may constitute a promising approach for combating castrate-resistant prostate cancer, for which there is no efficacious treatment.

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