Biology subjects

Gandarias, L.

Publications and source records attributed to Gandarias, L..

3 recordsLinked to original sources

bioRxiv2025

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

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

cell biology↗

bioRxiv2025

Chemical coupling of biological magnetosomes with amine-functionalized therapeutic antibody conjugates

BackgroundImmunotherapy, particularly in cancer treatment, can be enhanced using antibody-drug or antibody-radionuclide conjugates. These conjugates disrupt cell signaling and induce cell death, requiring the targeted antigen to be highly expressed on tumor cells to avoid damage to healthy tissues. A promising strategy to improve delivery is the use of magnetosomes, biological magnetic nanoparticles, which can be guided to tumor sites using magnetic fields. However, most antibody-drug or antibody-radionuclide conjugates are functionalized using the antibody amine groups of the lysine residues on the heavy chains. Therefore, these amine groups are no longer available to bind the antibodies to the magnetosomes. ResultsHere, we explore an alternative approach to bind amine-functionalized antibodies to magnetosomes. Using SulfoSuccinimidyl-4-(N-Maleimidomethyl)Cyclohexane-1-Carboxylate (S-SMCC) as a crosslinker, the antibodies are chemically attached to the magnetosome membrane via thiol groups through antibody partial reduction. Our results demonstrate that this chemical process preserves the integrity and functionality of both magnetosomes and antibodies. Moreover, we prove that the produced magnetosome-antibody conjugates are stable under various in vivo-like conditions. ConclusionThis coupling method offers significant advantages, enabling the coupling of therapeutic molecules to antibodies combined with the magnetic properties of magnetosomes. This new strategy aims to improve cancer therapy through targeted delivery and rapid accumulation at tumor sites.

bioengineering↗

bioRxiv2023

Intracellular biotransformation and disposal mechanisms of magnetosomes in macrophages and cancer cells

Magnetosomes are magnetite nanoparticles biosynthesized by magnetotactic bacteria. Given their potential clinical applications for the diagnosis and treatment of cancer, it is essential to understand what becomes of them once they are within the body. With this aim, here we have followed the intracellular long-term fate of magnetosomes in two cell types: cancer cells (A549 cell line), because they are the actual target for the therapeutic activity of the magnetosomes, and macrophages (RAW 264.7 cell line), because of their role at capturing foreign agents. We show that cells dispose of magnetosomes using three mechanisms: splitting them into daughter cells, excreting them to the surrounding environment, and degrading them yielding less or non-magnetic iron products. A deeper insight into the degradation mechanisms by means of time-resolved X-ray absorption near-edge structure (XANES) spectroscopy has allowed us to follow the intracellular biotransformation of magnetosomes by identifying and quantifying the iron species occurring during the process. In both cell types there is a first oxidation of magnetite to maghemite and then, earlier in macrophages than in cancer cells, ferrihydrite starts to appear. Given that ferrihydrite is the iron mineral phase stored in the cores of ferritin proteins, this suggests that cells use the iron released from the degradation of magnetosomes to load ferritin. Comparison of both cellular types evidences that macrophages are more efficient at disposing of magnetosomes than cancer cells, attributed to their role in degrading external debris and in iron homeostasis. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/532722v3_ufig1.gif" ALT="Figure 1"> View larger version (32K): org.highwire.dtl.DTLVardef@1b0d41dorg.highwire.dtl.DTLVardef@35ebf9org.highwire.dtl.DTLVardef@172a97org.highwire.dtl.DTLVardef@ed58ff_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗