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Targeting tumors with cyclic RGD-conjugated lipid nanoparticles loaded with an IR780 NIR dye: In vitro and in vivo evaluation

Publié le 29 mars 2018
Targeting tumors with cyclic RGD-conjugated lipid nanoparticles loaded with an IR780 NIR dye: In vitro and in vivo evaluation
Auteurs
Choi J., Rustique E., Henry M., Guidetti M., Josserand V., Sancey L., Boutet J., Coll J.-L.
Year2017-0483
Source-TitleInternational Journal of Pharmaceutics
Affiliations
Institute for Advanced Biosciences, INSERM U1209, CNRS UMR 5309, Université Grenoble Alpes, Grenoble, France, CEA, LETI, MINATEC Campus, Technologies for Biology and Health Division, 17 Avenue des Martyrs, Grenoble, France
Abstract
Like several 50 nm-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 av?3. We demonstrate a specific targeting of the receptor with cRGD-LNPs but not with cRAD-LNP and standard LNP using HEK293(?3), HEK293(?3)-?vRFP, DU145 and PC3 cell lines. We also demonstrate that cRGD-LNPs bind to ?v?3, interfere with cell adhesion to vitronectin and co-internalize with ?v?3 within 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. © 2017 Elsevier B.V.
Author-Keywords
Cancer imaging, Integrins, Nanoemulsion, NIR imaging, RGD, Theranostic
Index-Keywords
alanine, arginylglycylaspartic acid, contrast medium, glycine, ir 780, nanoparticle, unclassified drug, vitronectin, vitronectin receptor, animal experiment, animal model, Article, cell adhesion, cell contact, cell membrane, cell suspension, chemical structure, conjugation, controlled study, dispersity, embryo, ex vivo study, flow cytometry, fluorescence imaging, human, human cell, in vitro study, in vivo study, internalization, mouse, nonhuman, priority journal, reaction analysis, zeta potential
ISSN3785173
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