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bioRxiv · 10.1101/2025.11.26.690460

Identifying the internalization pathways of magnetotactic bacteria and magnetosomes by cancer cells

Gandarias, L.·Arana, L.·Gubieda, A. G.·Perez-Berna, A. J.·Abad-Diaz-de-Cerio, A.·Fdez-Gubieda, M. L.·Muela, A.·Garcia-Prieto, A.
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Abstract

Given the need for new tumor treatment strategies, therapies using magnetic nanoparticles and bacteria are gaining momentum. In this context, magnetotactic bacteria and magnetosomes could act as theranostic agents for use in magnetic hyperthermia, targeted drug delivery, and magnetic resonance imaging. Thus, understanding their interaction with target cells is essential to ensure their theranostic efficiency. This study investigates the uptake of magnetotactic bacteria (MSR-1) and magnetosomes by lung carcinoma cells (A549). First, MSR-1 and magnetosomes are imaged inside A549 cells using cryo soft X-ray tomography, revealing the presence of MSR-1 and magnetosomes inside endosomes. Subsequently, the endocytosis pathways involved in the internalization of MSR-1 and magnetosomes by the cells are elucidated. It is observed that MSR-1 mainly enter cells by receptor-mediated endocytosis, as described previously for other intracellular bacteria. However, the endocytosis of magnetosomes occurs mainly via phagocytosis or macropinocytosis, probably due to the large size of the formed magnetosome clusters. These findings fill a key gap in our understanding of the internalization of MSR-1 bacteria and magnetosomes by lung carcinoma cells, and establish a method applicable to studying their internalization by other target cell types. Graphical AbstractMagnetotactic bacteria (Magnetospirillum gryphiswaldense MSR-1) and magnetosomes, which are proposed as cancer theranostic mediators, are imaged inside A549 cancer cells in 3D using cryo soft X-ray tomography. Moreover, the endocytosis pathways that the cells use to internalize MSR-1 and magnetosomes are elucidated. MSR-1 predominantly enter A549 cells via receptor-mediated endocytosis, while magnetosomes are preferentially internalized via receptor-independent endocytosis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=102 SRC="FIGDIR/small/690460v1_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@bbcac0org.highwire.dtl.DTLVardef@fc33d6org.highwire.dtl.DTLVardef@1af65aeorg.highwire.dtl.DTLVardef@3ca539_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Gandarias, L., Arana, L., Gubieda, A. G., Perez-Berna, A. J., Abad-Diaz-de-Cerio, A., Fdez-Gubieda, M. L., Muela, A., Garcia-Prieto, A.. 2025-11-30. Identifying the internalization pathways of magnetotactic bacteria and magnetosomes by cancer cells. https://doi.org/10.1101/2025.11.26.690460

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