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Accueil du site > Equipes > Vecteurs colloïdaux et transport tissulaire (B. Verrier) > Thématiques > Toxicité et biodistribution chez le poisson zèbre > Biodistribution and toxicity in the Zebrafish

Biodistribution and toxicity in the Zebrafish

Project leader(s) : D. Le Guellec, B. Verrier, E. Delaune

People involved in the project : S. Legaz, J. Resseguier, C. Primard

The mechanisms of particles capture by the tissues and their potential transport in the body can be apprehended through different biological models adapted (in vitro, in vivo), controlled and available in the laboratory. We have access to infrared camera for non-invasive observations on anesthetized animals through collaborations (Prof. S. Paul, GIMAP, Saint-Etienne and Dr. R. Le Grand, CEA, Fontenay-aux-Roses), using adapted particles labeled with an IR fluorophore.

However, these systems of observation in the whole animal may be limited in terms of sensitivity or depth of field. So we have chosen a new animal model, the Zebrafish (Danio rerio), more adapted to the study of the biodistribution of PLA nanoparticles across the individual. We are able to study the transport of particles administered orally by bathing the fish in a solution of fluorescent particles, but also to study the dispersed particles after their intravenous injection into three days post-fertilization larvae.

The larvae of Zebrafish are transparent, which allows their observation by fluorescence microscopy by a non-invasive method. Thanks to their small size, micro-sections of the whole organism can be made to study the distribution of particles in the various organs of the animal. We finally have access to transgenic strains of Zebrafish, such as Fli-GFP (in which the endothelial cells express green fluorescent protein, GFP) or Fms-cherry (in which the macrophages are labeled by a red fluorescent protein).

This model finally opens prospects for cytotoxic studies of our particulate systems and other molecules developed in the Unit.

Biodistribution of red-fluorescent PLA nanoparticles after their intravenous injection in a 3 days-post-fecundation Zebrafish. The image results from the superposition of two photographs, one of transmitted light microscopy and the second one of fluorescence (red). The white box indicates the location of the magnification presented by red fluorescence, and the asterisk indicates the site of particles injection.

References :

Development of the zebrafish myoseptum with emphasis on the myotendinous junction.
Charvet B, Malbouyres M, Pagnon-Minot A, Ruggiero F and Le Guellec D
2011 - Cell Tis. Res. 346, 439-449.

CKIP-1 regulates mammalian and zebrafish myoblast fusion.
Baas D, Caussanel-Boude S, Guiraud A, Calhabeu F, Delaune E, Pilot F, Chopin E, Machuca-Gayet I, Vernay A, Bertrand S, Rual JF, Jurdic P, Hill DE, Vidal M, Schaeffer L, Goillot E.
2012 - J Cell Sci. 125(Pt 16):3790-800.

Collaborations :

PRECI : Plateau de Recherche Expérimentale de Criblage in vivo
Animalerie poisson de la SFR BioSciences Gerland - Lyon Sud (US8 / UMS3444)
Contact : Laure BERNARD