title: Targeting CD44 receptor-positive lung tumors using polysaccharide-based nanocarriers: Influence of nanoparticle size and administration route.
abstract: New approaches that are more efficient and able to specifically reach lung tumors are needed. We developed new hyaluronan-based nanoparticles targeting CD44 receptors of two different sizes and compared their lung cancer cells targeting efficacy in vitro and in vivo. The nanoparticles' cellular uptake was dose-dependent, and specific to hyaluronan receptors, particularly CD44. The binding and internalization differed according to nanoparticle size. In vivo biodistribution studies in two orthotopic lung tumor models showed that intrapulmonary nebulized nanoparticles accumulated in lungs, but not in the tumor nodules. In contrast, despite a significant liver capture, intravenous injection led to a better accumulation of the nanoparticles in the lung tumors compared with the surrounding healthy lung tissues. We demonstrated that the hyaluronan-based nanoparticles size plays significant role in cellular uptake and biodistribution. Small nanoparticles showed active targeting of CD44-overexpressing tumors, suggesting that they could be used as drug-delivery system.
  
  
  BACKGROUND
  Combating cancers remains an important goal in clinical medicine. In this study, the authors investigated the ability of two hyaluronan-based nanoparticles targeting CD44 receptors to home in on lung cancer cells in an in-vivo orthotropic model. The preferential uptake of smaller sized nanoparticles via intravenous route has further enhanced the existing knowledge of future drug designs.
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France; Univ. Grenoble Alpes, Institut Albert Bonniot, Grenoble, France.
authors.forename: Victor
authors.initials: V
authors.lastname: Jeannot
authors.affiliation: CNRS UMR5629, Laboratoire de Chimie des Polymères Organiques, Pessac, France; Univ. Bordeaux, Bordeaux-INP, Grenoble, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Mazzaferro
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France; Univ. Grenoble Alpes, Institut Albert Bonniot, Grenoble, France; OPTIMAL small animal imaging facility, Grenoble, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Lavaud
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France; Univ. Grenoble Alpes, Institut Albert Bonniot, Grenoble, France.
authors.forename: Laetitia
authors.initials: L
authors.lastname: Vanwonterghem
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France; Univ. Grenoble Alpes, Institut Albert Bonniot, Grenoble, France; OPTIMAL small animal imaging facility, Grenoble, France.
authors.forename: Maxime
authors.initials: M
authors.lastname: Henry
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France; Univ. Grenoble Alpes, Institut Albert Bonniot, Grenoble, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Arboléas
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France; Univ. Grenoble Alpes, Institut Albert Bonniot, Grenoble, France; OPTIMAL small animal imaging facility, Grenoble, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Vollaire
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France; Univ. Grenoble Alpes, Institut Albert Bonniot, Grenoble, France; OPTIMAL small animal imaging facility, Grenoble, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Josserand
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France; Univ. Grenoble Alpes, Institut Albert Bonniot, Grenoble, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Coll
authors.affiliation: CNRS UMR5629, Laboratoire de Chimie des Polymères Organiques, Pessac, France; Univ. Bordeaux, Bordeaux-INP, Grenoble, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lecommandoux
authors.affiliation: CNRS UMR5629, Laboratoire de Chimie des Polymères Organiques, Pessac, France; Univ. Bordeaux, Bordeaux-INP, Grenoble, France. Electronic address: schatz@enscbp.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Schatz
authors.affiliation: INSERM U823, Institut Albert Bonniot, Grenoble, France; Univ. Grenoble Alpes, Institut Albert Bonniot, Grenoble, France. Electronic address: amandine.hurbin@inserm.fr.
authors.forename: Amandine
authors.initials: A
authors.lastname: Hurbin
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D004337:Drug Carriers; D016503:Drug Delivery Systems; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011134:Polysaccharides / Q000008:administration & dosage / Q000737:chemistry; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; C497483:CD44 protein, human; D004337:Drug Carriers; D018960:Hyaluronan Receptors; D011134:Polysaccharides; D006820:Hyaluronic Acid
keywords: Biodistribution; CD44; Hyaluronan; Lung cancer; Near-infrared optical imaging; Polymer nanoparticles