Oncotarget

Research Papers:

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 _ and Ilaria Cascone

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Oncotarget. 2017; 8:90108-90122. https://doi.org/10.18632/oncotarget.21441

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Abstract

Zoi Diamantopoulou1,*, Maud-Emmanuelle Gilles1,*, Maha Sader1, Mélissande Cossutta1, Benoit Vallée1, Claire Houppe1, Damien Habert1, Blandine Brissault2, Eric Leroy2, Federica Maione3, Enrico Giraudo3, Damien Destouches1, Jacques Penelle2, José Courty1,** and Ilaria Cascone1,**

1Laboratory of Growth, Reparation and Tissue Regeneration (CRRET), University of Paris Est, ERL-CNRS 9215, 94010 Créteil, France

2East Paris Institute of Chemistry and Materials Science, CNRS & University Paris-Est, 94320 Thiais, France

3Department of Oncological Sciences and Laboratory of Transgenic Mouse Models, Institute for Cancer Research and Treatment, University of Torino School of Medicine, I-10060 Candiolo, Torino, Italy

*These authors have contributed equally to this work

**These authors are considered as co-senior author

Correspondence to:

José Courty, email: courty@u-pec.fr

Keywords: nanoparticles, antitumour activity, polyplex, nucleolin, pancreatic ductal adenocarcinoma

Received: June 21, 2017    Accepted: August 27, 2017    Published: September 30, 2017

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 N6L-polyplexes 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.


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