title: Nonvasoconstrictive hemoglobin particles as oxygen carriers.
abstract: Artificial oxygen carriers, favorably hemoglobin-based oxygen carriers (HBOCs), are being investigated intensively during the last 30 years with the aim to develop a universal blood substitute. However, serious side effects mainly caused by vasoconstriction triggered by nitric oxide (NO) scavenging due to penetration of nanosized HBOCs through the endothelial gaps of the capillary walls and/or oxygen oversupply in the precapillary arterioles due to their low oxygen affinity led to failure of clinical trials and FDA disapproval. To avoid these effects, HBOCs with a size between 100 and 1000 nm and high oxygen affinity are needed. Here we present for the first time unique hemoglobin particles (HbPs) of around 700 nm with high oxygen affinity and low immunogenicity using a novel, highly effective, and simple technique. The fabrication procedure provides particles with a narrow size distribution and nearly uniform morphology. The content of hemoglobin (Hb) in the particles corresponded to 80% of the Hb content in native erythrocytes. Furthermore, we demonstrate a successful perfusion of isolated mouse glomeruli with concentrated HbP suspensions in vitro. A normal, nonvasoconstrictive behavior of the afferent arterioles is observed, suggesting no oxygen oversupply and limited NO scavenging by these particles, making them a highly promising blood substitute.
authors.affiliation: Institute of Transfusion Medicine and Berlin-Brandenburg Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin , Charitéplatz 1, 10117 Berlin, Germany.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xiong
authors.forename: Zhi Zhao
authors.initials: ZZ
authors.lastname: Liu
authors.forename: Radostina
authors.initials: R
authors.lastname: Georgieva
authors.forename: Kathrin
authors.initials: K
authors.lastname: Smuda
authors.forename: Axel
authors.initials: A
authors.lastname: Steffen
authors.forename: Mauricio
authors.initials: M
authors.lastname: Sendeski
authors.forename: Andreas
authors.initials: A
authors.lastname: Voigt
authors.forename: Andreas
authors.initials: A
authors.lastname: Patzak
authors.forename: Hans
authors.initials: H
authors.lastname: Bäumler
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism*; D015195:Drug Design; D006454:Hemoglobins / Q000737:chemistry* / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D051379:Mice; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure*; D010100:Oxygen / Q000737:chemistry* / Q000493:pharmacokinetics*; D010316:Particle Size; D014662:Vasoconstrictor Agents / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D006454:Hemoglobins; D053769:Nanocapsules; D014662:Vasoconstrictor Agents; D010100:Oxygen