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      Magnetic Accumulation of SPIONs under Arterial Flow Conditions: Effect of Serum and Red Blood Cells

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          Abstract

          Magnetic drug targeting utilizes an external magnetic field to target superparamagnetic iron oxide nanoparticles (SPIONs) and their cargo to the diseased vasculature regions. In the arteries, the flow conditions affect the behavior of magnetic particles and the efficacy of their accumulation. In order to estimate the magnetic capture of SPIONs in more physiological-like settings, we previously established an ex vivo model based on human umbilical cord arteries. The artery model was employed in our present studies in order to analyze the effects of the blood components on the efficacy of magnetic targeting, utilizing 2 types of SPIONs with different physicochemical characteristics. In the presence of freshly isolated human plasma or whole blood, a strong increase in iron content measured by AES was observed for both particle types along the artery wall, in parallel with clotting activation due to endogenous thrombin generation in plasma. Subsequent studies therefore utilized SPION suspensions in serum and washed red blood cells (RBCs) at hematocrit 50%. Interestingly, in contrast to cell culture medium suspensions, magnetic accumulation of circulating SPION-3 under the external magnet was achieved in the presence of RBCs. Taken together, our data shows that the presence of blood components affects, but does not prevent, the magnetic accumulation of circulating SPIONs.

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          Most cited references42

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          Analysis of nanoparticle delivery to tumours

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            How it all starts: Initiation of the clotting cascade.

            The plasma coagulation system in mammalian blood consists of a cascade of enzyme activation events in which serine proteases activate the proteins (proenzymes and procofactors) in the next step of the cascade via limited proteolysis. The ultimate outcome is the polymerization of fibrin and the activation of platelets, leading to a blood clot. This process is protective, as it prevents excessive blood loss following injury (normal hemostasis). Unfortunately, the blood clotting system can also lead to unwanted blood clots inside blood vessels (pathologic thrombosis), which is a leading cause of disability and death in the developed world. There are two main mechanisms for triggering the blood clotting, termed the tissue factor pathway and the contact pathway. Only one of these pathways (the tissue factor pathway) functions in normal hemostasis. Both pathways, however, are thought to contribute to thrombosis. An emerging concept is that the contact pathway functions in host pathogen defenses. This review focuses on how the initiation phase of the blood clotting cascade is regulated in both pathways, with a discussion of the contributions of these pathways to hemostasis versus thrombosis.
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              Shaping nano-/micro-particles for enhanced vascular interaction in laminar flows.

              Non-spherical nano-/micro-particles can drift laterally (hydrodynamic margination) in a linear laminar flow under the concurrent effect of hydrodynamic and inertial forces. Such a feature can be exploited in the rational design of particle-based intravascular and pulmonary delivery systems and for designing new flow fractioning systems for high-throughput particle separation. A general approach is presented to predict the marginating behavior of non-spherical particles. The lateral drift velocity is shown to depend on the particle Stokes number St(a) and to grow with the size, density and rotational inertia of the particle. Elongated particles, in particular, low aspect ratio discoidal particles, exhibit the largest propensity to marginate in a linear laminar flow. In the blood microcirculation, at low shear rates (S<100 s(-1)), non-spherical particles oscillate around their trajectory and margination can only be achieved through the application of external force fields (gravitational, magnetic); whereas for larger S (100 s(-1)
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                16 July 2019
                July 2019
                : 24
                : 14
                : 2588
                Affiliations
                Section of Experimental Oncology und Nanomedicine (SEON), ENT-Department, Universitätsklinikum Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg, 91054 Erlangen, Germany
                Author notes
                [* ]Correspondence: Iwona.Cicha@ 123456uk-erlangen.de or Iwona.Cicha@ 123456yahoo.com ; Tel.: +49-9131-8543953
                Article
                molecules-24-02588
                10.3390/molecules24142588
                6681042
                31315293
                72c4ff5d-fce9-433e-9637-7ab2dbfd7692
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 20 May 2019
                : 14 July 2019
                Categories
                Article

                spions,magnetic targeting,nanoparticle accumulation,ex vivo flow model,blood cells

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