title: Tumour targeting of lipid nanocapsules grafted with cRGD peptides.
abstract: Combining targeting to therapy remains a major challenge in cancer treatment. To address this subject, the surface of lipid nanocapsules (LNC) was modified by grafting cRGD peptides, which are known to be recognised by αvβ3 integrins expressed by tumour endothelium and cancer cells. Applicability of this LNC-cRGD in tumour targeting was first assessed in vitro by the use of U87MG glioma cells. Biodistribution and tumour accumulation of radiolabelled LNC-cRGD in vivo were then evaluated in mice bearing the same subcutaneous xenograft. Flow cytometry and confocal microscopy results revealed that the cRGD grafting improved binding and internalisation compared to negative control LNC-cRAD and blank LNC. The peptide-grafted LNC remained in the blood circulation up to 3h with reduced capture by the RES organs. Tumour accumulation of LNC-cRGD with respect to LNC-cRAD was significantly higher at 1-3h. These results show that cRGD grafted to LNC has created a promising tumour-targetable nanocarrier that could be used in cancer treatment.
authors.affiliation: LUNAM Université, Université d'Angers, INSERM U1066, Angers, France. Electronic address: samuli.hirsjarvi@univ-angers.fr.
authors.forename: Samuli
authors.initials: S
authors.lastname: Hirsjärvi
authors.affiliation: LUNAM Université, Université d'Angers, INSERM U1066, Angers, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Belloche
authors.affiliation: LUNAM Université, Université d'Angers, INSERM U1066, Angers, France.
authors.forename: François
authors.initials: F
authors.lastname: Hindré
authors.affiliation: LUNAM Université, Université d'Angers, INSERM U1066, Angers, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Garcion
authors.affiliation: LUNAM Université, Université d'Angers, INSERM U1066, Angers, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Benoit
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry* / Q000493:pharmacokinetics; D008819:Mice, Nude; D058990:Molecular Targeted Therapy; D053769:Nanocapsules / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D053769:Nanocapsules; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide
keywords: Biodistribution; Cellular uptake; Grafting; Lipid nanocapsules; Targeting; cRGD peptide