Multivalent cationic pseudopeptide polyplexes as a tool for cancer therapy

Zoi Diamantopoulou, Maud Emmanuelle Gilles, Maha Sader, Mélissande Cossutta, Benoit Vallée, Claire Houppe, Damien Habert, Blandine Brissault, Eric Leroy, Federica Maione, Enrico Giraudo, Damien Destouches, Jacques Penelle, José Courty, Ilaria Cascone

Research output: Contribution to journalArticle

Abstract

In this study, a novel anticancer reagent based on polyplexes nanoparticles was developed. These nanoparticles are obtained by mixing negatively charged polyelectrolytes with the antitumour cationically-charged pseudopeptide N6L. Using two in vivo experimental tumor pancreatic models based upon PANC-1 and mPDAC cells, we found that the antitumour activity of N6L is significantly raised via its incorporation in polyplexed nanoparticles. Study of the mechanism of action using affinity isolation and si-RNA experiments indicated that N6L-polyplexes are internalized through their interaction with nucleolin. In addition, using a very aggressive model of pancreatic cancer in which gemcitabine, a standard of care for this type of cancer, has a weak effect on tumour growth, we observed that N6Lpolyplexes administration has a stronger efficacy than gemcitabine. Biodistribution studies carried out in tumour-bearing mice indicated that N6L-polyplexes localises in tumour tissue, in agreement with its antitumour effect. These results support the idea that N6L nanoparticles could develop into a promising strategy for the treatment of cancer, especially hard-to-treat pancreatic cancers.

Original languageEnglish
Pages (from-to)90108-90122
Number of pages15
JournalOncotarget
Volume8
Issue number52
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • Antitumour activity
  • Nanoparticles
  • Nucleolin
  • Pancreatic ductal adenocarcinoma
  • Polyplex

ASJC Scopus subject areas

  • Oncology

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  • Cite this

    Diamantopoulou, Z., Gilles, M. E., Sader, M., Cossutta, M., Vallée, B., Houppe, C., Habert, D., Brissault, B., Leroy, E., Maione, F., Giraudo, E., Destouches, D., Penelle, J., Courty, J., & Cascone, I. (2017). Multivalent cationic pseudopeptide polyplexes as a tool for cancer therapy. Oncotarget, 8(52), 90108-90122. https://doi.org/10.18632/oncotarget.21441