Assessment of the targeting specificity of a fluorescent albumin conceived as a preclinical agent of the liver function

Autor: Michel Bessodes, Pascal Houzé, Johanne Seguin, Katia Lemdani, Nathalie Mignet, Rabah Gahoual, Daniel Scherman, Hugo Salmon
Přispěvatelé: Unité de Technologies Chimiques et Biologiques pour la Santé (UTCBS - UM 4 (UMR 8258 / U1022)), Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de pharmacologie chimique et génétique et d'imagerie (UPCGI - UMR 8151 / UMR_S 1022 ), Centre de recherche de Vitry-Alfortville, Rhone Poulenc SA, Laboratoire de Neurochimie, Hospices Civils de Lyon (HCL), Mignet, Nathalie, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Université Paris sciences et lettres (PSL), Service de biochimie métabolique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Faculté de Pharmacie de Paris (UPD5 Pharmacie), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP), Paris Sciences et Lettres (PSL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], PSL Research University (PSL)
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
[SDV]Life Sciences [q-bio]
Contrast Media
Lactose
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
[SPI.MAT]Engineering Sciences [physics]/Materials
chemistry.chemical_compound
Mice
MESH: Liver Neoplasms
[CHIM] Chemical Sciences
General Materials Science
Tissue Distribution
MESH: Animals
Mice
Inbred BALB C
medicine.diagnostic_test
Liver Neoplasms
Optical Imaging
[CHIM.MATE]Chemical Sciences/Material chemistry
Carbocyanines
Human serum albumin
Fluorescence
[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biophysics
[SDV] Life Sciences [q-bio]
medicine.anatomical_structure
Biochemistry
Liver
Hepatocyte
[PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph]
Female
MESH: Carbocyanines
medicine.drug
MESH: Cell Line
Tumor
MESH: Mice
Inbred BALB C
MESH: Serum Albumin
Context (language use)
[SDV.CAN]Life Sciences [q-bio]/Cancer
Flow cytometry
03 medical and health sciences
[CHIM.ANAL]Chemical Sciences/Analytical chemistry
Cell Line
Tumor
MESH: Contrast Media
medicine
MESH: Transplantation
Homologous
Animals
Humans
Transplantation
Homologous
[CHIM]Chemical Sciences
MESH: Lactose
[PHYS.PHYS.PHYS-INS-DET]Physics [physics]/Physics [physics]/Instrumentation and Detectors [physics.ins-det]
MESH: Tissue Distribution
MESH: Mice
Serum Albumin
MESH: Optical Imaging
MESH: Humans
Albumin
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
030104 developmental biology
chemistry
Liver function
MESH: Female
MESH: Liver
Zdroj: Nanoscale
Nanoscale, 2018, 10 (45), pp.21151-21160. ⟨10.1039/c8nr04163f⟩
Nanoscale, Royal Society of Chemistry, 2018, 10 (45), pp.21151-21160. ⟨10.1039/c8nr04163f⟩
ISSN: 2040-3364
2040-3372
DOI: 10.1039/c8nr04163f⟩
Popis: International audience; In the context of increasing liver diseases, no contrast agent is currently available in Europe and the United States to directly assess the liver function. Only neolactosylated human serum albumin is being clinically used in Asia. In order to perform preclinical studies in the context of liver diseases, we conceived a fluorescent lactosylated albumin for the quantification of liver functional cells (l-Cyal). Precise characterization was achieved in order to determine the amounts of lactose and Cyanine 5 (Cy5) coupled to the albumin. In addition, potential aggregation was characterized by asymmetrical flow field-flow fractionation hyphenated to multi-angle light scattering (AF4-MALS). The optimal functionalized albumin exhibited a mass greater than 87 kDa which corresponds to the addition of 34 lactose moieties per protein and 1-2 Cy5 labels. Also, no significant formation of aggregates could be identified due to the modification of the native albumin. In healthy mice, the accumulation of l-Cyal in the liver and its selectivity for hepatocyte cells were shown by optical imaging and flow cytometry. Administration of l-Cyal to mice bearing liver metastases showed a reduced signal in the liver related to a decrease in the number of hepatocytes. The l-Cyal bioimaging contrast agent could be particularly useful for assessing the state of liver related diseases.
Databáze: OpenAIRE
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