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J Biotechnol. 2014 Oct 10;187:1-9. doi: 10.1016/j.jbiotec.2014.07.008. Epub 2014 Jul 15.

In vivo biodistribution and oxygenation potential of a new generation of oxygen carrier.

Author information

1
Unité INSERM 1078, SFR 148 ScInBioS, Université de Bretagne Occidentale, Université Européenne de Bretagne, 46 rue Félix Le Dantec, CS51819, 29218 Brest Cedex 02, France; Plateforme SynNanoVect, SFR 148 ScInBioS, Université de Bretagne Occidentale, Faculté de Médecine, 22 rue Camille Desmoulins, 29200 Brest, France.
2
HEMARINA SA, Aéropôle centre, Biotechnopôle, 29600 Morlaix, France.
3
Unité INSERM 1030, Radiothérapie Moléculaire, Université Paris XI, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.
4
Unité de Pathologie Expérimentale, Institut Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif, France.
5
CHRU de Brest, Département de Prothèses, UFR Odontologie, Brest F29238, France.
6
Unité INSERM 1078, SFR 148 ScInBioS, Université de Bretagne Occidentale, Université Européenne de Bretagne, 46 rue Félix Le Dantec, CS51819, 29218 Brest Cedex 02, France; Plateforme SynNanoVect, SFR 148 ScInBioS, Université de Bretagne Occidentale, Faculté de Médecine, 22 rue Camille Desmoulins, 29200 Brest, France; DUMG, Université de Bretagne Occidentale, CHRU de Brest, service de biochimie et de pharmaco-toxicologie, 5 avenue du Maréchal Foch, 29200 Brest, France. Electronic address: Tristan.Montier@univ-brest.fr.

Abstract

Natural giant extracellular hemoglobins (Hbs) from polychaete annelids are currently actively investigated as promising oxygen carriers. Their powerful oxygenating ability and their safety have been demonstrated in preclinical studies, motivating their development for therapeutic and industrial applications. HEMARINA-M101 (M101) is derived from the marine invertebrate Arenicola marina. It is formulated as a manufactured product designated HEMOXYCarrier(®) (HEMARINA SA, France). The aim of the present study was to unveil the fate of M101 after a single intravenous (i.v.) injection in mice. For this purpose, M101 was tagged with a far-red fluorescent dye. Repeated non-invasive fluorescent imaging revealed a rapid diffusion of M101 in the whole body of animals, reaching all the examined organs such as brain, liver, lungs and ovaries. Functional M101 was circulating in bloodstream for several hours, without inducing any obvious side-effects. Last, a single i.v. injection of M101 in mice bearing human-derived subcutaneous tumors demonstrated the ability of this Hb to reduce hypoxia in poorly vascularized tissues, thus supporting the biological relevance of M101 oxygen release to vertebrate tissues. Altogether, these results further encourage the development of M101 as an oxygen carrying therapeutic.

KEYWORDS:

Arenicola marina; Biodistribution; Fluorescence; Natural extracellular hemoglobin; Tissue oxygenation

PMID:
25034433
DOI:
10.1016/j.jbiotec.2014.07.008
[Indexed for MEDLINE]

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