Treatment efficacy of DNA lipid nanocapsules and DNA multimodular systems after systemic administration in a human glioma model

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TitreTreatment efficacy of DNA lipid nanocapsules and DNA multimodular systems after systemic administration in a human glioma model
Type de publicationArticle de revue
AuteurDavid, Stephanie, Montier, Tristan, Carmoy, Nathalie, Resnier, Pauline , Clavreul, Anne , Mevel, M., Pitard, Bruno, Benoît, Jean-Pierre , Passirani-Malleret, Catherine
EditeurWiley
TypeArticle scientifique dans une revue à comité de lecture
Année2012
LangueAnglais
DateDécembre 2012
Numéro12
Pagination769-775
Volume14
Titre de la revueJournal of Gene Medicine
ISSN1099-498X
Résumé en anglais

Background

We previously developed different types of DNA nanocarriers for systemic administration. Recently, the biodistribution profiles of these intravenously administered nanocarriers, DNA lipid nanocapsules (LNCs) and different multimodular systems (MMS), were analysed in healthy mice using in vivo biofluorescence imaging.

Methods

In the present study, the experiments were performed in an ectopic human U87MG glioma model in nude mice. First, the biodistribution profiles of intravenously administered multimodular systems delivering a plasmid DNA with a luciferase cassette were analysed using in vivo biofluorescence imaging. Afterwards, a systemic treatment with two long circulating DNA nanocarriers, poly(ethylene glycol) (PEG) DNA LNCs and galactose (GAL) DNA MMS dioleylamin-succinyl paromomycin (DOSP) was performed on this glioma model using a plasmid encoding the herpes simplex virus thymidine kinase (HSV-tk) and subsequent ganciclovir (GCV) treatment.

Results

The biodistribution profiles of the different DNA nanocarriers on this glioma model were similar to those observed on healthy animals and varied in function of their cationic lipid composition and their surface characteristics. Furthermore, PEG DNA LNCs and GAL DNA MMS DOSP showed a specific accumulation and some luciferase expression in the tumour tissue. The systemic treatment using the HSV-tk/GCV approach showed a tumour growth reduction compared to the nontreated mice cohort.

Conclusions

These results are in good accordance with those obtained previously with PEG DNA LNCs in a human melanoma mouse model and highlight the potential use of GAL DNA MMS DOSP and PEG DNA LNCs as future therapeutics in glioma and other cancers. Copyright © 2012 John Wiley & Sons, Ltd.

URL de la noticehttp://okina.univ-angers.fr/publications/ua3652
DOI10.1002/jgm.2683
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http://onlinelibrary.wiley.com/doi/10.1002/jgm.2683/abstract;jsessionid=...