Surface Modification of Hemoglobin-Based Oxygen Carriers Reduces Recognition by Haptoglobin, Immunoglobulin, and Hemoglobin Antibodies

Abstract

Hemoglobin-based oxygen carriers (HBOCs) represent a propitious type of blood substitute to transport oxygen throughout the body while acting as a carrier in biomedical applications. However, HBOCs in blood are recognized and rapidly scavenged by the body’s innate immune systems. To overcome this problem, HBOCs require a surface modification that provides protection against detection and elimination in order to prolong their circulation time after administration. In this study, we investigated different surface modifications of hemoglobin submicron particles (HbMPs) by double/triple precipitation, as well as by adsorption of human serum albumin (HSA), hyaluronic acid (HA), and pluronic (Plu) to discover how diverse surface modifications influence the oxygen binding capacity and the binding of anti-hemoglobin (Hb) antibodies, immunoglobulin G (IgG), and haptoglobin (HP) to HbMPs. The particle size and zeta potential of the six types of HbMP modifications were analyzed by zeta sizer, confocal laser scanning microscopy, and transmission electron microscopy (TEM), and were compared to the unmodified HbMPs. The results revealed that all surface-modified HbMPs had a submicron size with a negative charge. A slight decrease in the oxygen binding capacity was noticed. The specific binding of anti-Hb antibodies, IgG, and HP to all surface-modified HbMPs was reduced. This indicates a coating design able to protect the particles from detection and elimination processes by the immune system, and should lead to a delayed clearance and the required and essential increase in half-life in circulation of these particles in order to fulfill their purpose. Our surface modification method reflects a promising strategy for submicron particle design, and can lead the way toward novel biomedical applications.

Sonication Effectively Reduces Nanoparticle Size in Hemoglobin-Based Oxygen Carriers (HBOCs) Produced Through Coprecipitation: Implications for Red Blood Cell Substitutes

“…Unfortunately, a limitation of Hb particles synthesized through the CCD process is the relatively large particle diameter, with typical size distributions ranging from 700 to 1000 nm. 18 While some techniques, such as electrospray, have resulted in Hb nanoparticles in a consistently smaller size range, the low throughput creates challenges for production at clinically relevant scales. 19 The molecular diameters of HBOCs are critical to their in vivo performance.…”

“…This process allows for a large amount of Hb to be encapsulated in the inorganic template, demonstrating a Hb loading capacity of 80% of that found in an RBC. ,, This encapsulation strategy imparts high O 2 carrying capacity which, in turn, provides a stronger rationale for the Hb particle to function as an RBC substitute. Unfortunately, a limitation of Hb particles synthesized through the CCD process is the relatively large particle diameter, with typical size distributions ranging from 700 to 1000 nm . While some techniques, such as electrospray, have resulted in Hb nanoparticles in a consistently smaller size range, the low throughput creates challenges for production at clinically relevant scales …”

Künstliche Sauerstofftransporter können mehr als Sauerstoff liefern

“…Eine Interaktion von Hp mit HbMP konnte nahezu vollständig unterbunden werden, wenn die Hämoglobinpartikel durch Albumin bzw. Hyaluronsäure abgedeckt wurden [104]. Die lange Zeit gültige Annahme, dass eine Internalisierung von Hämoglobin durch CD163 ausschließlich durch die Komplexbildung mit Haptoglobin ausgelöst werden kann, scheint nach den Ergebnissen von Buehler et al sowie Schaer et al fraglich.…”

Bacterial safety study of the production process of hemoglobin-based oxygen carriers

“…For example, enzyme particles have been produced to be used as microreactors or biosensors [ 4 ]. This method can also represent a promising approach to the production of drug carriers by the precipitation of favorable biopolymers and corresponding surface modifications [ 5 – 6 ]. Thus, it was possible to immobilize vitamin B2 (riboflavin) in these particles together with human serum albumin (HSA).…”