Biocompatibility study of plyethylenglycol-coated iron oxide nanoparticles in human blood components

Abstract

Nanoparticles are used in a wide range of applications, including diagnostics, drug delivery, and the development of targeted therapies. Because of their small size, they can interact with biological molecules at the cellular and molecular levels, opening new possibilities for the treatment and prevention of diseases. In previous work, we synthesized and characterized polyethylene glycol-coated iron oxide nanoparticles (MAG@PEG), which exhibit magnetic properties along with favorable size, shape, and hydrodynamic diameter, making them suitable nanocarriers for biomedical applications. Based on in vitro cytotoxicity studies, we demonstrated that MAG@PEG is a safe nanosystem. Since intravenous administration is the most efficient route to deliver magnetic nanoparticles to target tissues, in this study we further investigated their hemocompatibility by evaluating the hemostatic and thrombogenic effects of MAG@PEG in human blood. All experiments were carried out using blood or plasma from volunteers who provided informed consent. For hemolysis assays, anticoagulated human blood was incubated with different MAG@PEG concentrations for one hour at 37°C, and hemoglobin release from red blood cells was spectrophotometrically measured at 540 nm. Results showed hemolysis rates below 2% under all tested conditions compared with the control, indicating that the nanosystem is non-hemolytic. Additionally, optical microscopy of blood smears from each condition showed that red blood cells maintained normal morphology across all samples. Conversely, incubation of whole non-anticoagulated blood with MAG@PEG shortened clot formation time. H&E-stained histological sections of the resulting clots revealed platelets and a fibrin network associated with nanoparticles. Coagulation factor analyses, including activated partial thromboplastin time (APTT), fibrinogen, thrombin, and thromboplastin in human plasma, showed no significant differences between treated and control conditions. However, at higher nanoparticle concentrations, APTT was prolonged, suggesting that the intrinsic coagulation pathway might be affected. Altogether, these results indicate that the MAG@PEG nanosystem exhibits good hemocompatibility, with negligible hemolytic activity and only a moderate impact on the intrinsic coagulation pathway at high concentrations, supporting their potential for safe intravenous use in biomedical applications.