Abstract
Intravascular application of magnetic nanocarriers is a critical step in the development of new therapeutic strategies, including magnetic drug targeting or hyperthermia. However, injection of particulate matter bears the intrinsic risk of contact activation of the blood coagulation cascade. In this work, we use point-of-care assays to study coagulation dynamics and clotting parameters in blood samples exposed to relevant concentrations of surface-functionalized carbon-coated iron carbide nanomagnets using unmodified nanomagnets and poly(ethylene)glycol-functionalized nanomagnets with different end-groups, including -OCH3, -NH2, -COOH, -IgG, and -ProteinA-protected-IgG (-IgG-ProtA). Silica nanoparticles with a comparable surface area are used as a reference material. For magnetic nanoparticles, we observe a decrease in clotting time by 25% compared to native blood at concentrations of 1 mg mL-1, independent of the surface functionalization, and only minor differences in receptor expression on platelets (GP-IIb-IIIa, CD62, and CD63) relative to control samples were observed. Interestingly, the inter-subject variance of the clotting time is similar to the nanoparticle-induced effect in a single subject with average clotting time. Whilst the present study is based on in vitro assays and a small group of healthy blood donors, the comparison to broadly used silica nanoparticles, and the fact that experimental intergroup variability is comparable to the observed effects from the carbon-coated nanomagnets suggests continuing investigations on their potential clinical use.
Highlights
Magnetic nanoparticles and nanoparticle-based materials offer attractive opportunities for the development of new therapeutic strategies in targeted drug delivery, magnetic separation-based blood puri cation, or as magnetic eld-driven arti cial muscles.[1,2,3,4,5,6] Nanomaterial-based approaches may revolutionize e.g., today's cancer treatment strategies by speci c destruction of pathogenic cells either by targeted delivery of chemotherapeutics or by inducing hyperthermic conditions through magnetic heating.[7]
The synthesis of magnetic nanoparticles with a metal core protected by a carbon shell has only recently been achieved and gives access to magnetic carriers with improved magnetic properties, extending both targeting and hyperthermia applications.[8,9]
We focus on interactions of surface-functionalized carbon-coated iron carbide magnetic nanoparticles with the blood coagulation system
Summary
Magnetic nanoparticles and nanoparticle-based materials offer attractive opportunities for the development of new therapeutic strategies in targeted drug delivery, magnetic separation-based blood puri cation, or as magnetic eld-driven arti cial muscles.[1,2,3,4,5,6] Nanomaterial-based approaches may revolutionize e.g., today's cancer treatment strategies by speci c destruction of pathogenic cells either by targeted delivery of chemotherapeutics or by inducing hyperthermic conditions through magnetic heating.[7] The synthesis of magnetic nanoparticles with a metal core protected by a carbon shell has only recently been achieved and gives access to magnetic carriers with improved magnetic properties (saturation magnetizations up to three times higher than commonly used metal oxide particles), extending both targeting and hyperthermia applications.[8,9] opportunities in therapy and diagnostics are numerous, detailed risk evaluations are critical in order to prevent costly downstream corrections.[10] Intravascular exposure to foreign matter, unless optimally biocompatible, induces a complex defence response of blood components, the vessel wall and other exposed tissues.[11] Injection of particulate matter, e.g. nano-sized particles (having a high speci c surface area), bears the intrinsic risk of contact activation of the blood coagulation cascade (Fig. 1).[12,13,14] Over the recent years, it has been recognized that a range of nanoparticulate carbon-based materials in uence blood coagulation and may potentially increase thrombogenic risk.[9,10,11,12,13,14,15]
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