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

Till L Hennig,Iwona Cicha,Stefan Lyer,Christoph Alexiou,Harald Unterweger

doi:10.3390/molecules24142588

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.

Highlights

Nanomedicine offers a unique platform for novel drug delivery approaches to the therapy of cardiovascular diseases (CVD)
We investigated the magnetic targeting of superparamagnetic iron oxide nanoparticles (SPIONs) suspended in cell culture media under various external magnetic field gradients and flow conditions, showing that accumulation of some types of SPIONs at the arterial wall is achievable under the guidance of a sufficiently strong external magnet
To answer the need for an easy to handle basic research model system for magnetic drug targeting (MDT) investigations under arterial flow conditions, we previously developed and reported an ex vivo model based on the branch-free human umbilical cord arteries (Figure A1)

Summary

Introduction

Nanomedicine offers a unique platform for novel drug delivery approaches to the therapy of cardiovascular diseases (CVD). Clinical impact of nanomedicine in diagnosis or therapy of CVD has been scarce, despite intensive research efforts [1,2]. One reason for this is an insufficient accumulation of nanoparticles in the diseased arteries [3]. Due to the larger size of the vessels, the rheological behavior of blood cells in the arterial flow differs from that in the microvessels [4,5,6]. Red blood cell (RBC) accumulation in the center of the lumen and the formation of rouleaux, creates a cell-free layer at the vessel wall, which may strongly affect the margination of nano-sized particles [7]. Previous studies showed that in flowing blood suspensions, platelets [8] and platelet-sized beads with 2.38 μm diameter [9]

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