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.