Initial interaction of citrate-coated iron oxide nanoparticles with the glycocalyx of THP-1 monocytes assessed by real-time magnetic particle spectroscopy and electron microscopy

Wolfram C Poller,Antje Ludwig,Norbert Löwa,Agnieszka Münster-Wandowski,Matthias Taupitz,Frank Wiekhorst,Verena Stangl,Moritz Schleicher

doi:10.1038/s41598-020-60162-8

Abstract

Interaction with biological material can alter physicochemical parameters of magnetic nanoparticles and might thereby change their magnetic behavior with potentially important implications for various nanoparticle applications. Little is known about changes of the magnetic behavior that occur during the initial phase of cell binding and uptake. We investigate the magnetic behavior of very small superparamagnetic iron-oxide nanoparticles (VSOP) during initial contact with THP-1 monocytes. We combine real-time magnetic particle spectroscopy (MPS), a fast and sensitive method for specific detection of magnetic nanoparticles in biological specimen with high-pressure-freezing/freeze-substitution transmission electron microscopy (HPF/FS-TEM), enabling us to generate snapshots of the interaction of VSOP with the cellular glycocalyx. MPS reveals significant changes of the dynamic magnetic behavior within seconds after VSOP injection into monocyte suspensions that correlate with the formation of nanoparticle clusters in the glycocalyx. The combination of real-time MPS and HPF/FS-TEM provides an ideal platform to analyze magnetic behaviors of nanoparticles upon interaction with cells and tissues.

Highlights

Interaction with biological material can alter physicochemical parameters of magnetic nanoparticles and might thereby change their magnetic behavior with potentially important implications for various nanoparticle applications
The shape of the Magnetic particle spectroscopy (MPS) spectrum, represented by the ratio of the fifth A5 to the third A3 harmonic amplitude, remains constant within the examined concentration range at 6%. This further indicates that the dynamic magnetic behavior is not affected by changing concentrations of very small superparamagnetic iron-oxide nanoparticles (VSOP), which is a pre-condition for a real-time in situ MPS monitoring of VSOP during incubation with THP-1 cells
In this study we observed a significant change of the dynamic magnetic behavior of VSOP during the initial contact of VSOP with THP-1 monocytes that correlated with compartmentalization and clustering of the nanoparticles in the glycocalyx

Summary

Introduction

Interaction with biological material can alter physicochemical parameters of magnetic nanoparticles and might thereby change their magnetic behavior with potentially important implications for various nanoparticle applications. Magnetic iron oxide nanoparticles (MNP) serve in a broad spectrum of biomedical applications ranging from hyperthermia treatment of cancer over targeted drug delivery to contrast enhancement in magnetic resonance imaging (MRI) because of their special magnetic behavior in external magnetic fields[1] This behavior is determined by the magnetic properties of MNP, which mostly depend on their composition, structure and size of the core. Using MPS we have previously observed changes of the dynamic magnetic behavior of citrate-coated very small superparamagnetic iron oxide nanoparticles (VSOP), which have entered the clinical development up to phase II trials as a contrast agent for MRI17, during incubation with THP-1 monocytes[2]. This structure was neglected, but recently it has been recognized how decisive the GCX is for cellular bioprocesses (e.g. cell migration, proliferation, adhesion) and for the uptake of nanoparticles[20,21,22]

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