title: Targeting tumors with cyclic RGD-conjugated lipid nanoparticles loaded with an IR780 NIR dye: In vitro and in vivo evaluation.
abstract: Like several 50nm-large nanocarriers, lipid nanoparticles (LNPs) can passively accumulate in tumors through the Enhanced Permeability and Retention (EPR) effect. In this study, we developed PEGylated LNPs loaded with IR780 iodide as a contrast agent for NIR fluorescence imaging and modified them with cyclic RGD peptides in order to target integrin avβ3. We demonstrate a specific targeting of the receptor with cRGD-LNPs but not with cRAD-LNP and standard LNP using HEK293(β3), HEK293(β3)-αvRFP, DU145 and PC3 cell lines. We also demonstrate that cRGD-LNPs bind to αvβ3, interfere with cell adhesion to vitronectin and co-internalize with αvβ3within one hour. We then investigated their biodistribution and tumor targeting in mice bearing DU145 or M21 tumors. We observed no significant differences between cRGD-LNP and the non-targeted ones regarding their biodistribution and accumulation/retention in tumors. This suggested that despite an efficient formulation of the cRGD-LNPs, the cRGD-mediated targeting was not increasing the total amount of LNP that can already accumulate passively in the subcutaneous tumors via the EPR effect.
authors.affiliation: Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France.
authors.forename: Jungyoon
authors.initials: J
authors.lastname: Choi
authors.affiliation: CEA, LETI, MINATEC Campus, Technologies for Biology and Health Division,17 Avenue des Martyrs, 38054 Grenoble, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Rustique
authors.affiliation: Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Henry
authors.affiliation: Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Guidetti
authors.affiliation: Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Josserand
authors.affiliation: Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Sancey
authors.affiliation: CEA, LETI, MINATEC Campus, Technologies for Biology and Health Division,17 Avenue des Martyrs, 38054 Grenoble, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Boutet
authors.affiliation: Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, 38000 Grenoble, France. Electronic address: Jean-luc.coll@univ-grenoble-alpes.fr.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Coll
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009369:Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism; D010456:Peptides, Cyclic / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D019096:Vitronectin / Q000378:metabolism
chemical_list: C548458:2-(2-(2-chloro-3-((1,3-dihydro-3,3-dimethyl-1-propyl-2H-indol-2-ylidene)ethylidene)-1-cyclohexen-1-yl)ethenyl)-3,3-dimethyl-1-propylindolium; D003287:Contrast Media; D007211:Indoles; D039302:Integrin alphaVbeta3; D008055:Lipids; D010456:Peptides, Cyclic; D019096:Vitronectin; C507169:cyclic arginine-glycine-aspartic acid peptide
keywords: Cancer imaging; Integrins; NIR imaging; Nanoemulsion; RGD; Theranostic