title: Cell tolerability and biodistribution in mice of indocyanine green-loaded lipid nanoparticles.
abstract: Considering toxicity requirements for clinical translation of fluorescence imaging applications, the use of biocompatible carriers for designing near infrared emitting contrast agents appears as an attractive alternative to semiconductor nanocrystals. Lipid nanoparticles (LNP) have been designed to serve as carriers for indocyanine green (ICG), the presently only human-use approved near infrared dye. The cytotoxicity and hemocompatibility of these nanoparticle-based probes are determined in vitro, respectively in mouse 3T3 fibroblasts and human blood samples. Comparative biodistribution of free ICG and ICG-LNP in mice is monitored, and an ex vivo fluorescence organ quantification is performed considering large animal cohorts. Good tolerability and very low hemolytic activity are demonstrated for naked and ICG-loaded LNP. Interestingly, ICG-LNP lead to long-term plasma fluorescence (> 24 hours) but also a partial intestinal reabsorption of ICG between 5 and 24 hours after injection. This novel ICG nanoformulation is foreseen to expand rapidly the field of clinical fluorescence imaging applications.
authors.affiliation: CEA, LETI, MINATEC, 17 rue des Martyrs, F38054 Grenoble cedex 9, France.
authors.forename: Fabrice P
authors.initials: FP
authors.lastname: Navarro
authors.forename: Frédérique
authors.initials: F
authors.lastname: Mittler
authors.forename: Michel
authors.initials: M
authors.lastname: Berger
authors.forename: Véronique
authors.initials: V
authors.lastname: Josserand
authors.forename: Julien
authors.initials: J
authors.lastname: Gravier
authors.forename: Françoise
authors.initials: F
authors.lastname: Vinet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Texier
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D005453:Fluorescence; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007208:Indocyanine Green / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D008055:Lipids / Q000737:chemistry / Q000493:pharmacokinetics* / Q000633:toxicity*; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity; D014018:Tissue Distribution
chemical_list: D008055:Lipids; D007208:Indocyanine Green