title: In vivo imaging of DNA lipid nanocapsules after systemic administration in a melanoma mouse model.
abstract: The biodistribution of intravenously injected DNA lipid nanocapsules (DNA LNCs), encapsulating pHSV-tk, was analysed by in vivo imaging on an orthotopic melanoma mouse model and by a subsequent treatment with ganciclovir (GCV), using the gene-directed enzyme prodrug therapy (GDEPT) approach. Luminescent melanoma cells, implanted subcutaneously in the right flank of the mice, allowed us to follow tumour growth and tumour localisation with in vivo bioluminescence imaging (BLI). In parallel, DNA LNCs or PEG DNA LNCs (DNA LNCs recovered with PEG(2000)) encapsulating a fluorescent probe, DiD, allowed us to follow their biodistribution with in vivo biofluorescence imaging (BFI). The BF-images confirmed a prolonged circulation-time for PEG DNA LNCs as was previously observed on an ectotopic model of glioma; comparison with BL-images evidenced the colocalisation of PEG DNA LNCs and melanoma cells. After these promising results, treatment with PEG DNA LNCs and GCV on a few animals was performed and the treatment efficacy measured by BLI. The first results showed tumour growth reduction tendency and, once optimised, this therapy strategy could become a new option for melanoma treatment.
authors: LUNAM Université - Ingénierie de la Vectorisation Particulaire, F-49933 Angers, France.
authors: Stephanie
authors: S
authors: David
authors: Nathalie
authors: N
authors: Carmoy
authors: Pauline
authors: P
authors: Resnier
authors: Caroline
authors: C
authors: Denis
authors: Laurent
authors: L
authors: Misery
authors: Bruno
authors: B
authors: Pitard
authors: Jean-Pierre
authors: JP
authors: Benoit
authors: Catherine
authors: C
authors: Passirani
authors: Tristan
authors: T
authors: Montier
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000008:administration & dosage / Q000378:metabolism; D002232:Carbocyanines / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D004247:DNA / Q000008:administration & dosage*; D004587:Electrophoresis, Agar Gel; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D015774:Ganciclovir / Q000627:therapeutic use; D018014:Gene Transfer Techniques; D041722:Genes, Transgenic, Suicide / Q000235:genetics*; D005990:Glycerol / Q000031:analogs & derivatives / Q000737:chemistry; D006561:Herpes Simplex / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D058950:Melanoma-Specific Antigens / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D053769:Nanocapsules / Q000737:chemistry*; D017830:Octoxynol / Q000737:chemistry; D009829:Oleic Acids / Q000737:chemistry; D010316:Particle Size; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D011092:Polyethylene Glycols / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D055672:Static Electricity; D013229:Stearic Acids / Q000737:chemistry; D013499:Surface Properties; D013937:Thymidine Kinase / Q000235:genetics; D014018:Tissue Distribution; D016896:Treatment Outcome; D014280:Triglycerides / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D052160:Benzothiazoles; D002232:Carbocyanines; C532924:D-luciferin; D005229:Fatty Acids, Monounsaturated; D005456:Fluorescent Dyes; D008055:Lipids; D058950:Melanoma-Specific Antigens; D053769:Nanocapsules; D009829:Oleic Acids; D010714:Phosphatidylethanolamines; D000644:Quaternary Ammonium Compounds; D013229:Stearic Acids; D014280:Triglycerides; C480531:polyglyceryl-6-dioleate; D011092:Polyethylene Glycols; C024286:3,3'-dioctadecylindocarbocyanine; C067028:Solutol HS 15; D017830:Octoxynol; D004247:DNA; D008156:Luciferases; D013937:Thymidine Kinase; C070046:1,2-dioleoyloxy-3-(trimethylammonium)propane; D015774:Ganciclovir; D005990:Glycerol