Hematotoxicity of magnetite nanoparticles coated with polyethylene glycol: in vitro and in vivo studies

Abstract

Hematotoxicity of magnetite nanoparticles coated with dimercaptosuccinic acid (DMSA) and polyethylene glycol (PEG) has been evaluated by determining their safety in vitro and in vivo in a rat model up to 30 days after administration of a single dose. The in vitro analysis consists of global plasma coagulation (PT, aPTT, and fibrinogen) and platelet aggregation tests while the hematotoxicity studies in vivo include a complete blood count and the possible genotoxic effect analysis in the bone marrow hematopoietic function. Prolonged aPTT values indicate a higher anticoagulant effect for NP-DMSA compared with PEG-coated nanoparticles as a consequence of the higher surface charge of the former. The in vivo tests showed that these bioferrofluids do not cause genotoxic effects, affect erythropoiesis or increase the number of immature erythrocytes in the bone marrow at the analyzed dose. However, nanoparticle administration showed a significant effect on the leukocyte counts in animals treated with DMSA coated nanoparticles 24 h after injection. This response is not observed in animals treated with PEG modified nanoparticles which justifies the use of this polymer in biomasking strategies.

Effects of cerium oxide nanoparticles on hemostasis: Coagulation, platelets, and vascular endothelial cells

“…Many studies showed that physicochemical properties of NPs can also induce destruction of erythrocytes with release of hemoglobin, leading to anemia and other pathological conditions . One of the mechanisms that plays a crucial role in hemolysis is the oxidative damage to erythrocyte membrane, rich of polyunsaturated fatty acids .…”

“…This slight decrease, that did not influence blood coagulation, as showed by APTT and PT tests, could be due to processes of absorption and/or binding of fibrinogen on NC surface, as observed in other studies investigating the affinity of plasma proteins for different NP surfaces. 36,37 Many studies showed that physicochemical properties of NPs can also induce destruction of erythrocytes with release of hemoglobin, 38,39 leading to anemia and other pathological conditions. 40 One of the mechanisms that plays a crucial role in hemolysis is the oxidative damage to erythrocyte membrane, rich of polyunsaturated fatty acids.…”

The effect of size and surface ligands of iron oxide nanoparticles on blood compatibility

“…Moreover, some researchers evaluated the haematotoxicity of magnetic nanoparticles coated with dimercaptosuccinic acid (DMSA) and polyethylene glycol (PEG) in vitro and in vivo in a rat model. 19 In vitro analyses revealed prolonged APTT (activated partial thromboplastin time) values for DMSA compared with PEGcoated nanoparticles. There was a signicant effect on the leukocyte counts in animals treated with DMSA-coated nanoparticles compared with the PEG-modied group.…”

Ultra-Small Superparamagnetic Iron-Oxide Nanoparticles Exert Different Effects on Erythrocytes in Normotensive and Hypertensive Rats

“…Nevertheless, it was suggested that nanoparticle administration might lead to cell damage; however, while using PEG-coated nanoparticles, no signs of hemolysis, genotoxic effects, or modulation of erythropoiesis were detected in female Wistar rats. PEG-coated nanoparticles do not have an impact on leukocyte count; thus are preferred [ 21 ]. However, PEG was shown to have an immunogenic effect, which may lead to faster clearance and lower target tissue accumulation [ 22 ].…”