1. Lectin recognition and hepatocyte endocytosis of GalNAc-decorated nanostructured lipid carriers
- Author
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Mireille Chevallet, Franck Fieschi, Francois Bulteau Bulteau, Christelle Gateau, Pascale Delangle, Aurélien Deniaud, Michel Thépaut, Isabelle Texier, Laura Gauthier, Corinne Vivès, Chimie Interface Biologie pour l’Environnement, la Santé et la Toxicologie (CIBEST ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Département Microtechnologies pour la Biologie et la Santé (DTBS), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Métaux et Organes (MET&OR), Laboratoire de Chimie et Biologie des Métaux (LCBM - UMR 5249), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), and ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)
- Subjects
Acetylgalactosamine ,surface functionalisation ,N-acetylgalactosamine ,nanostructured lipid carriers ,Pharmaceutical Science ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,02 engineering and technology ,Endocytosis ,macrophage galactose-lectin ,targeted drug delivery ,N-Acetylgalactosamine ,03 medical and health sciences ,chemistry.chemical_compound ,asialoglycoprotein receptor ,0302 clinical medicine ,Lectins ,medicine ,Humans ,Drug Carriers ,biology ,Lectin ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Hep G2 Cells ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,021001 nanoscience & nanotechnology ,Lipids ,Nanostructures ,Cell biology ,carbohydrates (lipids) ,medicine.anatomical_structure ,chemistry ,Targeted drug delivery ,030220 oncology & carcinogenesis ,Hepatocyte ,Drug delivery ,biology.protein ,hepatocytes ,lipids (amino acids, peptides, and proteins) ,Asialoglycoprotein receptor ,Nanocarriers ,0210 nano-technology - Abstract
International audience; Liver is the main organ for metabolism but is also subject to various pathologies, from viral, genetic, cancer or metabolic origin. There is thus a crucial need to develop efficient liver-targeted drug delivery strategies. Asialoglycoprotein receptor (ASGPR) is a C-type lectin expressed in the hepatocyte plasma membrane that efficiently endocytoses glycoproteins exposing galactose (Gal) or N-acetylgalactosamine (GalNAc). Its targeting has been successfully used to drive the uptake of small molecules decorated with three or four GalNAc, thanks to an optimisation of their spatial arrangement. Herein, we assessed the biological properties of highly stable nanostructured lipid carriers (NLC) made of FDA-approved ingredients and formulated with increasing amounts of GalNAc. Cellular studies showed that a high density of GalNAc was required to favour hepatocyte internalisation via the ASGPR pathway. Interaction studies using surface plasmon resonance and the macrophage galactose-lectin as GalNAc-recognising lectin confirmed the need of high GalNAc density for specific recognition of these NLC. This work is the first step for the development of efficient nanocarriers for prolonged liver delivery of active compounds.
- Published
- 2020
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