Shell matters: Magnetic targeting of SPIONs and in vitro effects on endothelial and monocytic cell function

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) are versatile and easily functionalized agents with high potential for diagnostic and therapeutic intravascular applications. In this study, we analyzed the responses of endothelial (ECs) and monocytic cells to three different types of SPIONs, in order to assess the influence of physico-chemical properties on the biological reactions to SPIONs. The following formulations were used: (1) Lauric acid-coated and BSA-stabilized SPION-1,(2) Lauric acid/BSA-coated SPION-2 and (3) dextran-coated SPION-3. SPION-1 were strongly internalized by ECs and reduced their viability in static conditions. Additionally, they had a dose-dependent inhibitory effect on monocytic cell chemotaxis to MCP-1, but did not affect monocytic cell recruitment by ECs. SPION-2 uptake was less pronounced, both in ECs and monocytic cells, and these particles were better tolerated by the vascular cells. Not being internalized by endothelial or monocytic cells, SPION-3 did not induce relevant effects on cell viability, motility or endothelial-monocytic cell interactions.Taken together, localized accumulation of circulating SPION under physiologic-like flow conditions and their cellular uptake depends on the physicochemical characteristics. Our findings suggest that SPION-2 are suitable for magnetic targeting of atherosclerotic plaques. Due to their excellent biocompatibility and low internalization, SPION-3 may represent a suitable imaging agent for intravascular applications.

A novel human artery model to assess the magnetic accumulation of SPIONs under flow conditions

“…The considerable differences in the physicochemical properties of SPIONs resulted in dramatic differences of their magnetic accumulation under flow conditions, as also shown in our previous in vitro studies 16 . Out of the three types of SPIONs tested in the ex vivo artery model, SPION-1 had by far the largest capacity to accumulate at the artery segment placed directly under the tip of the magnet, corresponding to the magnetic field gradient of about 40 T/m at the artery centre ( Fig.…”

“… 20 . In support of their hypothesis, a successful accumulation of circulating SPIONs under external magnets has been demonstrated in several in vitro models of straight 21 22 and bifurcating channels 16 23 24 . Furthermore, our previous experimental ex vivo work in bovine arteries 14 25 showed that accumulation of flowing SPIONs in the arterial wall is achievable under the guidance of a sufficiently strong external magnet, as confirmed by histology, microCT and magnetorelaxometry 14 26 .…”

“… 20 , this enhanced tendency to form aggregates results in an increased magnetic targeting of SPION-1 clusters under arterial flow conditions. Despite the fact that these particles constitute a very good model nanosystem for evaluation of various parameters influencing the magnetic capture under flow conditions, SPION-1 being characterised by the tendency to agglomerate, enhanced cellular uptake and relatively high endothelial toxicity 16 , are not a candidate for further development and potential clinical use. For clinical applications, especially nanoparticle agglomeration may be a decisive factor limiting their use in patients, as it affects both safety and bioavailability.…”

Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging

“…27 Compared to the previously marketed dextran-coated contrast agent ferumoxides, SPIONdex have several distinct and improved characteristics. Ferumoxides was composed of magnetite nanoparticles with iron concentration 11.2 mg/mL, hydrodynamic diameter 120-150 nm, and zeta potential -13 mV.…”

Selection of potential iron oxide nanoparticles for breast cancer treatment based on in vitro cytotoxicity and cellular uptake

“…46 In our in vitro experiments, the probability of a partial sedimentation during cell culture experiments is higher with SPION LA followed by SPION LA-HSA and SPION Dex , which possibly results in higher SPION LA uptake and toxicity. To what extent sedimentation of these SPIONs influences dose-response curves 47 and how the uptake and toxicity can affect the in vivo administration are difficult to foresee. Models and methodologies for particle dosimetry that enables the determination of the dosage delivered to cells have already been presented, and it has been shown that usage of the cellular dose rather than administered dose improves the correlation between dose and response to particles in vitro and in vivo.…”