[Paper Review] 3D-Imaging and Quantification of Magnetic Nanoparticle Uptake by Living Cells

Hendrik Paysen, Norbert Loewa+8 more|arXiv (Cornell University)|Dec 3, 2019

Characterization and Applications of Magnetic Nanoparticles45 references17 citations

TL;DR

This study demonstrates 3D magnetic particle imaging (MPI) for real-time, quantitative tracking of magnetic nanoparticle (MNP) uptake by living cells, leveraging changes in MNP dynamics during cellular internalization. The method distinguishes free from cell-bound MNPs with a mean relative difference of 23.8% in quantification, validated by phenanthroline assay, offering a non-invasive tool for studying cellular processes and early inflammatory disease diagnosis.

ABSTRACT

Magnetic particle imaging (MPI) is a non-invasive, non-ionizing imaging technique for the visualization and quantification of magnetic nanoparticles (MNPs). The technique is especially suitable for cell imaging as it offers zero background contribution from the surrounding tissue, high sensitivity, and good spatial and temporal resolutions. Previous studies have demonstrated that the dynamic magnetic behaviour of MNPs changes during cellular binding and internalization. In this study, we demonstrate how this information is encoded in the MPI imaging signal. Through MPI imaging we are able to discriminate between free and cell-bound MNPs in reconstructed images. This technique was used to image and quantify the changes that occur in-vitro when free MNPs come into contact with cells and undergo cellularuptake over time. The quantitative MPI results were verified by a phenanthroline assay. The results showed a mean relative difference of 23.8% for the quantification of cell-bound MNPs. The insights gained from such observations provide a new window into fundamental biological processes and associated pathological changes occurring at a cellular level. This technique could therefore offer new opportunities for the early diagnosis of inflammatory diseases.

Motivation & Objective

• To develop a non-invasive, non-ionizing method for visualizing and quantifying magnetic nanoparticle (MNP) uptake by living cells.
• To exploit changes in MNP dynamics during cellular binding and internalization as a signal for distinguishing free from cell-bound MNPs in MPI.
• To validate MPI-based quantification of cell-bound MNPs against a standard phenanthroline assay.
• To provide a 3D imaging approach with high spatial and temporal resolution for studying fundamental cellular processes.
• To explore the potential of MPI for early diagnosis of inflammatory diseases through cellular-level monitoring.

Proposed method

• Utilized magnetic particle imaging (MPI) to acquire 3D images of MNPs in live cells, capitalizing on the technique's zero background signal from biological tissue.
• Leveraged the dynamic magnetic behavior of MNPs—specifically changes in their relaxation dynamics during cellular binding and internalization—as a signal source for discrimination.
• Reconstructed 3D MPI images to spatially resolve MNP distribution and quantify uptake over time in vitro.
• Applied a phenanthroline assay as a gold-standard reference method to validate MPI-derived quantification of cell-bound MNPs.
• Used a custom MPI scanner to acquire time-resolved data, enabling kinetic analysis of MNP uptake dynamics.
• Analyzed signal intensity changes in MPI data correlated with MNP binding states to infer cellular uptake progression.

Experimental results

Research questions

• RQ1 Can MPI distinguish between free and cell-bound magnetic nanoparticles in living cells based on their dynamic magnetic behavior?
• RQ2 How accurately can MPI quantify the amount of MNP uptake by cells over time compared to established biochemical assays?
• RQ3 What is the temporal evolution of MNP uptake in vitro, and how does it correlate with changes in MNP magnetic dynamics?
• RQ4 To what extent does MPI provide high-resolution 3D visualization of MNP distribution during cellular internalization?
• RQ5 Can MPI serve as a viable tool for monitoring cellular processes linked to inflammation, based on MNP uptake kinetics?

Key findings

• MPI successfully differentiated between free and cell-bound magnetic nanoparticles in 3D images by detecting changes in their dynamic magnetic behavior.
• The mean relative difference between MPI quantification and phenanthroline assay results was 23.8% for cell-bound MNP levels, indicating moderate but measurable agreement.
• Time-resolved MPI imaging revealed the kinetic progression of MNP uptake by cells over time, demonstrating the method's temporal resolution.
• The technique achieved high sensitivity and spatial resolution, with no background signal from biological tissue, enabling clear visualization of MNP distribution.
• The observed signal changes in MPI corresponded to MNP internalization, confirming that dynamic magnetic properties encode uptake information.
• The study establishes a foundation for using MPI as a non-invasive tool to study cellular processes and detect early pathological changes, such as in inflammation.