TY - JOUR
T1 - In vivo biodistribution and oxygenation potential of a new generation of oxygen carrier
AU - Le Gall, Tony
AU - Polard, Valérie
AU - Rousselot, Morgane
AU - Lotte, Auréline
AU - Raouane, Mouna
AU - Lehn, Pierre
AU - Opolon, Paule
AU - Leize, Elisabeth
AU - Deutsch, Eric
AU - Zal, Franck
AU - Montier, Tristan
N1 - Funding Information:
The authors thank Alain Frautel (H2P2 platform, Rennes), Céline Galipo, and Yann Sibiril (INSERM 1078, Brest) for their technical contribution and Pr. Paul Alain Jaffrès (CNRS 6521, Brest) for his expertise in chemistry. This work was supported by grants from VLM, AFM, “Ligue contre le cancer”, “Association de Transfusion Sanguine et de Biogénétique Gaétan Saleün”, “Conseil Régional de Bretagne”, and “Brest Métropole Océane”.
PY - 2014/10/10
Y1 - 2014/10/10
N2 - 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.
AB - 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.
KW - Arenicola marina
KW - Biodistribution
KW - Fluorescence
KW - Natural extracellular hemoglobin
KW - Tissue oxygenation
UR - http://www.scopus.com/inward/record.url?scp=84905234354&partnerID=8YFLogxK
U2 - 10.1016/j.jbiotec.2014.07.008
DO - 10.1016/j.jbiotec.2014.07.008
M3 - Article
C2 - 25034433
AN - SCOPUS:84905234354
SN - 0168-1656
VL - 187
SP - 1
EP - 9
JO - Journal of Biotechnology
JF - Journal of Biotechnology
ER -