title: Comparative biodistribution in mice of cyanine dyes loaded in lipid nanoparticles.
abstract: Two near infrared cyanine dyes, DiD (1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine perchlorate) and ICG (Indocyanine Green) were loaded in lipid nanoparticles (LNP). DiD-LNP and ICG-LNP presented similar physicochemical characteristics (hydrodynamic diameter, polydispersity, zeta potential), encapsulation efficiency, and colloidal stability when stored in PBS buffer. However, whereas DiD had similar biodistribution than cholesteryl-1-(14)C-oleate ([(14)C]CHO, a constituent of the nanoparticle used as a reference radiotracer), ICG displayed a different biodistribution pattern, similar to that of the free dye, indicative of its immediate leakage from the nanovector after blood injection. NMR spectroscopy using Proton NOE (Nuclear Overhauser Effect) measurements showed that the localization of the dye in the lipid nanoparticles was slightly different: ICG, more amphiphilic than DiD, was found both inside the lipid core and at particle interface, whereas DiD, more hydrophobic, appeared exclusively located inside the particle core. The ICG release rate from the particles was 7% per 1 month under storage conditions (4 °C, dark, 10% of lipids), whereas no leakage could be detected for DiD. ICG leakage increased considerably in the presence of BSA 40 g/L (45% leakage in 24h at 100 mg/mL of lipids), because of the high affinity of the fluorophore for plasma proteins. On the contrary, no DiD leakage was observed, until high dilution of the nanoparticles which triggered their dissociation (45% leakage in 24h at 1 mg/mL of lipids). Altogether, the subtle difference in dye localization into the nanoparticles, the partial dissociation of the LNP in diluted media, and more importantly the high ICG affinity for plasma proteins, accounted for the differences observed in the fluorescence biodistribution after tail vein injection of the dye-loaded nanoparticles.
authors: Université Grenoble Alpes, F-38000 Grenoble, France; CEA-LETI MINATEC/ DTBS, 17 avenue des Martyrs, F-38054 Grenoble Cedex 9, France; SHFJ, CEA Orsay, 4 place Général Leclerc, 91401 Orsay Cedex, France; INSERM UMR 970, PARCC, Université Paris Descartes, Sorbonne Paris Cité, France; Assistance Publique des Hopitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
authors: Juliette
authors: J
authors: Mérian
authors: SHFJ, CEA Orsay, 4 place Général Leclerc, 91401 Orsay Cedex, France.
authors: Raphaël
authors: R
authors: Boisgard
authors: Université Grenoble Alpes, INAC-SCIB, LRM, F-38000 Grenoble, France; CEA, INAC-SCIB, LRM, F-38054 Grenoble, France.
authors: Pierre-Alain
authors: PA
authors: Bayle
authors: Université Grenoble Alpes, INAC-SCIB, LRM, F-38000 Grenoble, France; CEA, INAC-SCIB, LRM, F-38054 Grenoble, France.
authors: Michel
authors: M
authors: Bardet
authors: INSERM UMR 970, PARCC, Université Paris Descartes, Sorbonne Paris Cité, France; Assistance Publique des Hopitaux de Paris, Hôpital Européen Georges Pompidou, Paris, France.
authors: Bertrand
authors: B
authors: Tavitian
authors: Université Grenoble Alpes, F-38000 Grenoble, France; CEA-LETI MINATEC/ DTBS, 17 avenue des Martyrs, F-38054 Grenoble Cedex 9, France. Electronic address: isabelle.texier-nogues@cea.fr.
authors: Isabelle
authors: I
authors: Texier
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D004337:Drug Carriers; D005260:Female; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D057927:Hydrophobic and Hydrophilic Interactions; D007208:Indocyanine Green / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D011485:Protein Binding; D066244:Proton Magnetic Resonance Spectroscopy; D012710:Serum Albumin, Bovine / Q000378:metabolism; D012995:Solubility; D014018:Tissue Distribution
chemical_list: D002232:Carbocyanines; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008055:Lipids; D012710:Serum Albumin, Bovine; D007208:Indocyanine Green
keywords: Biodistribution; Cyanine dyes; Fluorescence imaging; Lipid nanoparticles; Nanomedicine; Payload localization; Radiotracer