Dual Labeling of Primary Cells with Fluorescent Gadolinium Oxide Nanoparticles

Nadine Brune; Benedikt Mues; Eva Miriam Buhl; Kai-Wolfgang Hintzen; Stefan Jockenhoevel; Christian G Cornelissen; Ioana Slabu; Anja Lena Thiebes

doi:10.3390/nano13121869

Dual Labeling of Primary Cells with Fluorescent Gadolinium Oxide Nanoparticles

Nanomaterials (Basel). 2023 Jun 16;13(12):1869. doi: 10.3390/nano13121869.

Authors

Nadine Brune¹, Benedikt Mues¹, Eva Miriam Buhl², Kai-Wolfgang Hintzen^{1

3}, Stefan Jockenhoevel^{1

4}, Christian G Cornelissen^{1

5}, Ioana Slabu¹, Anja Lena Thiebes^{1

4}

Affiliations

¹ Institute of Applied Medical Engineering, Helmholtz Institute, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany.
² Institute of Pathology, Electron Microscopy Facility, University Clinic Aachen, 52074 Aachen, Germany.
³ DWI-Leibniz-Institute for Interactive Materials, 52074 Aachen, Germany.
⁴ Aachen-Maastricht Institute for Biobased Materials, Faculty of Science and Engineering, Maastricht University, 6167 RD Geleen, The Netherlands.
⁵ Department of Pneumology and Internal Intensive Care Medicine, Medical Clinic V, University Clinic Aachen, 52074 Aachen, Germany.

Abstract

The interest in mesenchymal stromal cells as a therapy option is increasing rapidly. To improve their implementation, location, and distribution, the properties of these must be investigated. Therefore, cells can be labeled with nanoparticles as a dual contrast agent for fluorescence and magnetic resonance imaging (MRI). In this study, a more efficient protocol for an easy synthesis of rose bengal-dextran-coated gadolinium oxide (Gd₂O₃-dex-RB) nanoparticles within only 4 h was established. Nanoparticles were characterized by zeta potential measurements, photometric measurements, fluorescence and transmission electron microscopy, and MRI. In vitro cell experiments with SK-MEL-28 and primary adipose-derived mesenchymal stromal cells (ASC), nanoparticle internalization, fluorescence and MRI properties, and cell proliferation were performed. The synthesis of Gd₂O₃-dex-RB nanoparticles was successful, and they were proven to show adequate signaling in fluorescence microscopy and MRI. Nanoparticles were internalized into SK-MEL-28 and ASC via endocytosis. Labeled cells showed sufficient fluorescence and MRI signal. Labeling concentrations of up to 4 mM and 8 mM for ASC and SK-MEL-28, respectively, did not interfere with cell viability and proliferation. Gd₂O₃-dex-RB nanoparticles are a feasible contrast agent to track cells via fluorescence microscopy and MRI. Fluorescence microscopy is a suitable method to track cells in in vitro experiments with smaller samples.

Keywords: adipose-derived mesenchymal stromal cells (ASC); contrast agent; dextran; magnetic resonance imaging (MRI); rose bengal.

Abstract

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