title: Treatment efficacy of DNA lipid nanocapsules and DNA multimodular systems after systemic administration in a human glioma model.
abstract: 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.
authors.affiliation: LUNAM Université - Equipe MINT: micro et nanomédecines biomimétiques, IBS-CHU, 4 rue Larrey, 49933, Angers Cedex 9, France.
authors.forename: Stephanie
authors.initials: S
authors.lastname: David
authors.forename: Tristan
authors.initials: T
authors.lastname: Montier
authors.forename: Nathalie
authors.initials: N
authors.lastname: Carmoy
authors.forename: Pauline
authors.initials: P
authors.lastname: Resnier
authors.forename: Anne
authors.initials: A
authors.lastname: Clavreul
authors.forename: Mathieu
authors.initials: M
authors.lastname: Mével
authors.forename: Bruno
authors.initials: B
authors.lastname: Pitard
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Benoit
authors.forename: Catherine
authors.initials: C
authors.lastname: Passirani
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D018014:Gene Transfer Techniques; D005910:Glioma / Q000235:genetics / Q000628:therapy*; D006801:Humans; D008055:Lipids / Q000737:chemistry; D008081:Liposomes; D051379:Mice; D057054:Molecular Imaging; D053769:Nanocapsules; D010957:Plasmids; D011092:Polyethylene Glycols; D023041:Xenograft Model Antitumor Assays
chemical_list: D008055:Lipids; D008081:Liposomes; D053769:Nanocapsules; D011092:Polyethylene Glycols; D004247:DNA