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Edouard Alphandéry - One of the best experts on this subject based on the ideXlab platform.
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Applications of magnetotactic bacteria and Magnetosome for cancer treatment: A review emphasizing on practical and mechanistic aspects
Drug Discovery Today Biosilico, 2020Co-Authors: Edouard AlphandéryAbstract:Magnetotactic bacteria (MTB) synthesize iron oxide (Fe3O4) nanoparticles (NPs), called Magnetosomes, with large sizes leading to a ferrimagnetic behavior and a stable magnetic moment at physiological temperature, a chain structure that prevents NP aggregation and promotes uniform NP distribution, and a mineral core of magnetite/maghemite composition, which can be stabilized by an organic coating. Such properties can favor Magnetosome administration to humans under certain optimized non-toxic conditions of fabrication. In this review, I describe the fabrication methods, physico-chemical properties, and the anti-tumor activity of different types of MTB/Magnetosome preparations, highlighting the bio-compatibility and excellent anti-tumor activity of purified non-pyrogenic Magnetosome minerals stabilized by a synthetic chemical compound.
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A Method for Producing Highly Pure Magnetosomes in Large Quantity for Medical Applications Using Magnetospirillum gryphiswaldense MSR-1 Magnetotactic Bacteria Amplified in Minimal Growth Media
Frontiers in Bioengineering and Biotechnology, 2020Co-Authors: Clément Berny, François Guyot, Raphael Le Fèvre, Karine Blondeau, Christine Guizonne, Emilie Rousseau, Nicolas Bayan, Edouard AlphandéryAbstract:We report the synthesis in large quantity of highly pure Magnetosomes for medical applications. For that, Magnetosomes are produced by MSR-1 Magnetospirillum gryphiswaldense magnetotactic bacteria using minimal growth media devoid of uncharacterized and toxic products prohibited by pharmaceutical regulation, i.e., yeast extract, heavy metals different from iron, and carcinogenic, mutagenic and reprotoxic agents. This method follows two steps, during which bacteria are first pre-amplified without producing Magnetosomes and are then fed with an iron source to synthesize Magnetosomes, yielding, after 50 h of growth, an equivalent OD565 of ~8 and 10 mg of Magnetosomes in iron per liter of growth media. Compared with Magnetosomes produced in non-minimal growth media, those particles have lower concentrations in metals other than iron. Very significant reduction or disappearance in Magnetosome composition of zinc, manganese, barium, and aluminum are observed. This new synthesis method paves the way towards the production of Magnetosomes for medical applications.
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biodegraded Magnetosomes with reduced size and heating power maintain a persistent activity against intracranial u87 luc mouse gbm tumors
Journal of Nanobiotechnology, 2019Co-Authors: Edouard Alphandéry, François Guyot, Ahmed Idbaih, Clovis Adam, Jean-yves Delattre, Charlotte Schmitt, Florence Gazeau, Imène ChebbiAbstract:An important but rarely addressed question in nano-therapy is to know whether bio-degraded nanoparticles with reduced sizes and weakened heating power are able to maintain sufficient anti-tumor activity to fully eradicate a tumor, hence preventing tumor re-growth. To answer it, we studied Magnetosomes, which are nanoparticles synthesized by magnetotactic bacteria with sufficiently large sizes (~ 30 nm on average) to enable a follow-up of nanoparticle sizes/heating power variations under two different altering conditions that do not prevent anti-tumor activity, i.e. in vitro cellular internalization and in vivo intra-tumor stay for more than 30 days. When Magnetosomes are internalized in U87-Luc cells by being incubated with these cells during 24 h in vitro, the dominant Magnetosome sizes within the Magnetosome size distribution (DMS) and specific absorption rate (SAR) strongly decrease from DMS ~ 40 nm and SAR ~ 1234 W/gFe before internalization to DMS ~ 11 nm and SAR ~ 57 W/gFe after internalization, a behavior that does not prevent internalized Magnetosomes to efficiently destroy U87-Luc cell, i.e. the percentage of U87-Luc living cells incubated with Magnetosomes decreases by 25% between before and after alternating magnetic field (AMF) application. When 2 µl of a suspension containing 40 µg of Magnetosomes are administered to intracranial U87-Luc tumors of 2 mm3 and exposed (or not) to 15 magnetic sessions (MS), each one consisting in 30 min application of an AMF of 27 mT and 198 kHz, DMS and SAR decrease between before and after the 15 MS from ~ 40 nm and ~ 4 W/gFe down to ~ 29 nm and ~ 0 W/gFe. Although the Magnetosome heating power is weakened in vivo, i.e. no measurable tumor temperature increase is observed after the sixth MS, anti-tumor activity remains persistent up to the 15th MS, resulting in full tumor disappearance among 50% of treated mice. Here, we report sustained Magnetosome anti-tumor activity under conditions of significant Magnetosome size reduction and complete loss of Magnetosome heating power.
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Biodegraded Magnetosomes with reduced size and heating power maintain a persistent activity against intracranial U87-Luc mouse GBM tumors
Journal of Nanobiotechnology, 2019Co-Authors: Edouard Alphandéry, François Guyot, Ahmed Idbaih, Clovis Adam, Jean-yves Delattre, Charlotte Schmitt, Florence Gazeau, Imène ChebbiAbstract:BACKGROUND: An important but rarely addressed question in nano-therapy is to know whether bio-degraded nanoparticles with reduced sizes and weakened heating power are able to maintain sufficient anti-tumor activity to fully eradicate a tumor, hence preventing tumor re-growth. To answer it, we studied Magnetosomes, which are nanoparticles synthesized by magnetotactic bacteria with sufficiently large sizes (~ 30 nm on average) to enable a follow-up of nanoparticle sizes/heating power variations under two different altering conditions that do not prevent anti-tumor activity, i.e. in vitro cellular internalization and in vivo intra-tumor stay for more than 30 days. RESULTS: When Magnetosomes are internalized in U87-Luc cells by being incubated with these cells during 24 h in vitro, the dominant Magnetosome sizes within the Magnetosome size distribution (DMS) and specific absorption rate (SAR) strongly decrease from DMS ~ 40 nm and SAR ~ 1234 W/gFe before internalization to DMS ~ 11 nm and SAR ~ 57 W/gFe after internalization, a behavior that does not prevent internalized Magnetosomes to efficiently destroy U87-Luc cell, i.e. the percentage of U87-Luc living cells incubated with Magnetosomes decreases by 25% between before and after alternating magnetic field (AMF) application. When 2 µl of a suspension containing 40 µg of Magnetosomes are administered to intracranial U87-Luc tumors of 2 mm3 and exposed (or not) to 15 magnetic sessions (MS), each one consisting in 30 min application of an AMF of 27 mT and 198 kHz, DMS and SAR decrease between before and after the 15 MS from ~ 40 nm and ~ 4 W/gFe down to ~ 29 nm and ~ 0 W/gFe. Although the Magnetosome heating power is weakened in vivo, i.e. no measurable tumor temperature increase is observed after the sixth MS, anti-tumor activity remains persistent up to the 15th MS, resulting in full tumor disappearance among 50% of treated mice. CONCLUSION: Here, we report sustained Magnetosome anti-tumor activity under conditions of significant Magnetosome size reduction and complete loss of Magnetosome heating power.
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Magnetic-field induced rotation of Magnetosome chains in silicified magnetotactic bacteria
Scientific Reports, 2018Co-Authors: Marine Blondeau, Yohan Guyodo, François Guyot, Christophe Gatel, Nicolas Menguy, Imène Chebbi, Bernard Haye, Mickaël Durand-dubief, Edouard Alphandéry, Roberta BraynerAbstract:Understanding the biological processes enabling magnetotactic bacteria to maintain oriented chains of magnetic iron-bearing nanoparticles called Magnetosomes is a major challenge. The study aimed to constrain the role of an external applied magnetic field on the alignment of Magnetosome chains in Magnetospirillum magneticum AMB-1 magnetotactic bacteria immobilized within a hydrated silica matrix. A deviation of the chain orientation was evidenced, without significant impact on cell viability, which was preserved after the field was turned-off. Transmission electron microscopy showed that the crystallographic orientation of the nanoparticles within the chains were preserved. Off-axis electron holography evidenced that the change in Magnetosome orientation was accompanied by a shift from parallel to anti-parallel interactions between individual nanocrystals. The field-induced destructuration of the chain occurs according to two possible mechanisms: (i) each Magnetosome responds individually and reorients in the magnetic field direction and/or (ii) short Magnetosome chains deviate in the magnetic field direction. This work enlightens the strong dynamic character of the Magnetosome assembly and widens the potentialities of magnetotactic bacteria in bionanotechnology. Since their discovery more than 30 years ago, magnetotactic bacteria have received much attention in the fields of geological, chemical, physical and biological sciences 1-5. However, the processes by which they synthesize iron oxide (or sulphide) magnetic nanoparticles and organize them into chains allowing the cell to orient itself along the geomagnetic field are still far from being fully understood 6-10. It is well-admitted that production of the nano-crystals occurs in specialized organelles, called Magnetosomes, formed by a membrane invagination at multiple sites in the cell. However, identifying the proteins controlling nucleation, size, shape and arrangement in chains of the nanocrystals, as well as the mechanisms of action of these proteins, remains a challenging task 11-15. Phenotypic divergences between different species were evidenced 16. In some Magnetospirillum sp. strains, the chain is stabilized along the longitudinal axis of the cell by an organic filament, MamK protein, while the connection of Magnetosomes to this structure is provided by a protein MamJ 17,18. The deletion of MamK gene in Magnetospirillum gryphiswaldense MSR-1 leads to short chains separated by gaps devoid of Magnetosomes, while the deletion of MamJ induces aggregation of Magnetosomes within the cell with observable filaments not attached to the biogenic particles 19,20. In Magnetospirillum magneticum AMB-1, additional MamJ-like and MamK-like proteins were identified that are involved in the dynamic of the filament and the Magnetosome organization in chain 21-23. The capacity of the Magnetosome chain to act as a compass is not only related to the spatial arrangement of nanocrystals, but also to their crystallographic and magnetic alignment. In some magnetotactic bacteria (e.g., Magnetospirillum sp.), the biogenic magnetite nanoparticles have a cubo-octahedral morphology with a magnetic
Dirk Schüler - One of the best experts on this subject based on the ideXlab platform.
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Single-step transfer of biosynthetic operons endows a non-magnetotactic Magnetospirillum strain from wetland with Magnetosome biosynthesis.
Environmental microbiology, 2020Co-Authors: Marina V. Dziuba, René Uebe, Theresa Zwiener, Dirk SchülerAbstract:The magnetotactic lifestyle represents one of the most complex traits found in many bacteria from aquatic environments and depends on magnetic organelles, the Magnetosomes. Genetic transfer of Magnetosome biosynthesis operons to a non-magnetotactic bacterium has only been reported once so far, but it is unclear whether this may also occur in other recipients. Besides magnetotactic species from freshwater, the genus Magnetospirillum of the Alphaproteobacteria also comprises a number of strains lacking Magnetosomes, which are abundant in diverse microbial communities. Their close phylogenetic interrelationships raise the question whether the non-magnetotactic magnetospirilla may have the potential to (re)gain a magnetotactic lifestyle upon acquisition of Magnetosome gene clusters. Here, we studied the transfer of Magnetosome gene operons into several non-magnetotactic environmental magnetospirilla. Single-step transfer of a compact vector harbouring >30 major Magnetosome genes from M. gryphiswaldense induced Magnetosome biosynthesis in a Magnetospirillum strain from a constructed wetland. However, the resulting magnetic cellular alignment was insufficient for efficient magnetotaxis under conditions mimicking the weak geomagnetic field. Our work provides insights into possible evolutionary scenarios and potential limitations for the dissemination of magnetotaxis by horizontal gene transfer and expands the range of foreign recipients that can be genetically magnetized.
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Generation of nanomagnetic biocomposites by genetic engineering of bacterial Magnetosomes
Bioinspired Biomimetic and Nanobiomaterials, 2019Co-Authors: Frank Mickoleit, Dirk SchülerAbstract:Magnetosomes are magnetic nanoparticles biomineralized by magnetotactic bacteria. They consist of a monocrystalline magnetite core enveloped by the Magnetosome membrane, which harbors a set of spec...
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Preparation of Bacterial Magnetosomes for Proteome Analysis.
Methods in molecular biology (Clifton N.J.), 2018Co-Authors: Oliver Raschdorf, Dirk Schüler, René UebeAbstract:Magnetotactic bacteria form unique prokaryotic organelles, termed Magnetosomes, which consist of membrane-enclosed magnetite nanoparticles. Analysis of Magnetosome biogenesis has been greatly facilitated by proteomic methods. These, however, require pure, highly enriched Magnetosomes. Here, we describe the purification of Magnetosomes from Magnetospirillum gryphiswaldense using high pressure cell disruption, and sequential purification by magnetic enrichment and sucrose density ultracentrifugation. The resulting enriched Magnetosomes can be subsequently subjected to proteomic analyses or biotechnological applications.
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in vivo coating of bacterial magnetic nanoparticles by Magnetosome expression of spider silk inspired peptides
Biomacromolecules, 2018Co-Authors: Frank Mickoleit, Christian B Borkner, Mauricio Toronahuelpan, Heike M Herold, Denis S Maier, Juergen M Plitzko, Thomas Scheibel, Dirk SchülerAbstract:Magnetosomes are natural magnetic nanoparticles with exceptional properties that are synthesized in magnetotactic bacteria by a highly regulated biomineralization process. Their usability in many applications could be further improved by encapsulation in biocompatible polymers. In this study, we explored the production of spider silk-inspired peptides on Magnetosomes of the alphaproteobacterium Magnetospirillum gryphiswaldense. Genetic fusion of different silk sequence-like variants to abundant Magnetosome membrane proteins enhanced magnetite biomineralization and caused the formation of a proteinaceous capsule, which increased the colloidal stability of isolated particles. Furthermore, we show that spider silk peptides fused to a Magnetosome membrane protein can be used as seeds for silk fibril growth on the Magnetosome surface. In summary, we demonstrate that the combination of two different biogenic materials generates a genetically encoded hybrid composite with engineerable new properties and enhanced...
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Magnetosome biogenesis in magnetotactic bacteria
Nature Reviews Microbiology, 2016Co-Authors: René Uebe, Dirk SchülerAbstract:Magnetosomes are unique organelles that 'magnetize' bacteria. In this Review, Uebe and Schuler discuss our current understanding of the mechanisms of Magnetosome biogenesis, and consider how recent genetic advances in this area may lead to the development of exciting biotechnological applications. Magnetotactic bacteria derive their magnetic orientation from Magnetosomes, which are unique organelles that contain nanometre-sized crystals of magnetic iron minerals. Although these organelles have evident potential for exciting biotechnological applications, a lack of genetically tractable magnetotactic bacteria had hampered the development of such tools; however, in the past decade, genetic studies using two model Magnetospirillum species have revealed much about the mechanisms of Magnetosome biogenesis. In this Review, we highlight these new insights and place the molecular mechanisms of Magnetosome biogenesis in the context of the complex cell biology of Magnetospirillum spp. Furthermore, we discuss the diverse properties of Magnetosome biogenesis in other species of magnetotactic bacteria and consider the value of genetically 'magnetizing' non-magnetotactic bacteria. Finally, we discuss future prospects for this highly interdisciplinary and rapidly advancing field.
Imène Chebbi - One of the best experts on this subject based on the ideXlab platform.
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biodegraded Magnetosomes with reduced size and heating power maintain a persistent activity against intracranial u87 luc mouse gbm tumors
Journal of Nanobiotechnology, 2019Co-Authors: Edouard Alphandéry, François Guyot, Ahmed Idbaih, Clovis Adam, Jean-yves Delattre, Charlotte Schmitt, Florence Gazeau, Imène ChebbiAbstract:An important but rarely addressed question in nano-therapy is to know whether bio-degraded nanoparticles with reduced sizes and weakened heating power are able to maintain sufficient anti-tumor activity to fully eradicate a tumor, hence preventing tumor re-growth. To answer it, we studied Magnetosomes, which are nanoparticles synthesized by magnetotactic bacteria with sufficiently large sizes (~ 30 nm on average) to enable a follow-up of nanoparticle sizes/heating power variations under two different altering conditions that do not prevent anti-tumor activity, i.e. in vitro cellular internalization and in vivo intra-tumor stay for more than 30 days. When Magnetosomes are internalized in U87-Luc cells by being incubated with these cells during 24 h in vitro, the dominant Magnetosome sizes within the Magnetosome size distribution (DMS) and specific absorption rate (SAR) strongly decrease from DMS ~ 40 nm and SAR ~ 1234 W/gFe before internalization to DMS ~ 11 nm and SAR ~ 57 W/gFe after internalization, a behavior that does not prevent internalized Magnetosomes to efficiently destroy U87-Luc cell, i.e. the percentage of U87-Luc living cells incubated with Magnetosomes decreases by 25% between before and after alternating magnetic field (AMF) application. When 2 µl of a suspension containing 40 µg of Magnetosomes are administered to intracranial U87-Luc tumors of 2 mm3 and exposed (or not) to 15 magnetic sessions (MS), each one consisting in 30 min application of an AMF of 27 mT and 198 kHz, DMS and SAR decrease between before and after the 15 MS from ~ 40 nm and ~ 4 W/gFe down to ~ 29 nm and ~ 0 W/gFe. Although the Magnetosome heating power is weakened in vivo, i.e. no measurable tumor temperature increase is observed after the sixth MS, anti-tumor activity remains persistent up to the 15th MS, resulting in full tumor disappearance among 50% of treated mice. Here, we report sustained Magnetosome anti-tumor activity under conditions of significant Magnetosome size reduction and complete loss of Magnetosome heating power.
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Biodegraded Magnetosomes with reduced size and heating power maintain a persistent activity against intracranial U87-Luc mouse GBM tumors
Journal of Nanobiotechnology, 2019Co-Authors: Edouard Alphandéry, François Guyot, Ahmed Idbaih, Clovis Adam, Jean-yves Delattre, Charlotte Schmitt, Florence Gazeau, Imène ChebbiAbstract:BACKGROUND: An important but rarely addressed question in nano-therapy is to know whether bio-degraded nanoparticles with reduced sizes and weakened heating power are able to maintain sufficient anti-tumor activity to fully eradicate a tumor, hence preventing tumor re-growth. To answer it, we studied Magnetosomes, which are nanoparticles synthesized by magnetotactic bacteria with sufficiently large sizes (~ 30 nm on average) to enable a follow-up of nanoparticle sizes/heating power variations under two different altering conditions that do not prevent anti-tumor activity, i.e. in vitro cellular internalization and in vivo intra-tumor stay for more than 30 days. RESULTS: When Magnetosomes are internalized in U87-Luc cells by being incubated with these cells during 24 h in vitro, the dominant Magnetosome sizes within the Magnetosome size distribution (DMS) and specific absorption rate (SAR) strongly decrease from DMS ~ 40 nm and SAR ~ 1234 W/gFe before internalization to DMS ~ 11 nm and SAR ~ 57 W/gFe after internalization, a behavior that does not prevent internalized Magnetosomes to efficiently destroy U87-Luc cell, i.e. the percentage of U87-Luc living cells incubated with Magnetosomes decreases by 25% between before and after alternating magnetic field (AMF) application. When 2 µl of a suspension containing 40 µg of Magnetosomes are administered to intracranial U87-Luc tumors of 2 mm3 and exposed (or not) to 15 magnetic sessions (MS), each one consisting in 30 min application of an AMF of 27 mT and 198 kHz, DMS and SAR decrease between before and after the 15 MS from ~ 40 nm and ~ 4 W/gFe down to ~ 29 nm and ~ 0 W/gFe. Although the Magnetosome heating power is weakened in vivo, i.e. no measurable tumor temperature increase is observed after the sixth MS, anti-tumor activity remains persistent up to the 15th MS, resulting in full tumor disappearance among 50% of treated mice. CONCLUSION: Here, we report sustained Magnetosome anti-tumor activity under conditions of significant Magnetosome size reduction and complete loss of Magnetosome heating power.
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Magnetic-field induced rotation of Magnetosome chains in silicified magnetotactic bacteria
Scientific Reports, 2018Co-Authors: Marine Blondeau, Yohan Guyodo, François Guyot, Christophe Gatel, Nicolas Menguy, Imène Chebbi, Bernard Haye, Mickaël Durand-dubief, Edouard Alphandéry, Roberta BraynerAbstract:Understanding the biological processes enabling magnetotactic bacteria to maintain oriented chains of magnetic iron-bearing nanoparticles called Magnetosomes is a major challenge. The study aimed to constrain the role of an external applied magnetic field on the alignment of Magnetosome chains in Magnetospirillum magneticum AMB-1 magnetotactic bacteria immobilized within a hydrated silica matrix. A deviation of the chain orientation was evidenced, without significant impact on cell viability, which was preserved after the field was turned-off. Transmission electron microscopy showed that the crystallographic orientation of the nanoparticles within the chains were preserved. Off-axis electron holography evidenced that the change in Magnetosome orientation was accompanied by a shift from parallel to anti-parallel interactions between individual nanocrystals. The field-induced destructuration of the chain occurs according to two possible mechanisms: (i) each Magnetosome responds individually and reorients in the magnetic field direction and/or (ii) short Magnetosome chains deviate in the magnetic field direction. This work enlightens the strong dynamic character of the Magnetosome assembly and widens the potentialities of magnetotactic bacteria in bionanotechnology. Since their discovery more than 30 years ago, magnetotactic bacteria have received much attention in the fields of geological, chemical, physical and biological sciences 1-5. However, the processes by which they synthesize iron oxide (or sulphide) magnetic nanoparticles and organize them into chains allowing the cell to orient itself along the geomagnetic field are still far from being fully understood 6-10. It is well-admitted that production of the nano-crystals occurs in specialized organelles, called Magnetosomes, formed by a membrane invagination at multiple sites in the cell. However, identifying the proteins controlling nucleation, size, shape and arrangement in chains of the nanocrystals, as well as the mechanisms of action of these proteins, remains a challenging task 11-15. Phenotypic divergences between different species were evidenced 16. In some Magnetospirillum sp. strains, the chain is stabilized along the longitudinal axis of the cell by an organic filament, MamK protein, while the connection of Magnetosomes to this structure is provided by a protein MamJ 17,18. The deletion of MamK gene in Magnetospirillum gryphiswaldense MSR-1 leads to short chains separated by gaps devoid of Magnetosomes, while the deletion of MamJ induces aggregation of Magnetosomes within the cell with observable filaments not attached to the biogenic particles 19,20. In Magnetospirillum magneticum AMB-1, additional MamJ-like and MamK-like proteins were identified that are involved in the dynamic of the filament and the Magnetosome organization in chain 21-23. The capacity of the Magnetosome chain to act as a compass is not only related to the spatial arrangement of nanocrystals, but also to their crystallographic and magnetic alignment. In some magnetotactic bacteria (e.g., Magnetospirillum sp.), the biogenic magnetite nanoparticles have a cubo-octahedral morphology with a magnetic
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Biocompatible coated Magnetosome minerals with various organization and cellular interaction properties induce cytotoxicity towards RG-2 and GL-261 glioma cells in the presence of an alternating magnetic field
Journal of Nanobiotechnology, 2017Co-Authors: Yasmina Hamdous, François Guyot, Imène Chebbi, Chalani Mandawala, Raphael Le Fèvre, Olivier Seksek, Edouard AlphandéryAbstract:Background: Biologics magnetics nanoparticles, Magnetosomes, attract attention because of their magnetic characteristics and potential applications. The aim of the present study was to develop and characterize novel Magnetosomes, which were extracted from magnetotactic bacteria, purified to produce apyrogen Magnetosome minerals, and then coated with Chitosan, Neridronate, or Polyethyleneimine. It yielded stable Magnetosomes designated as M-Chi, M-Neri, and M-PEI, respectively. Nanoparticle biocompatibility was evaluated on mouse fibroblast cells (3T3), mouse glioblastoma cells (GL-261) and rat glioblastoma cells (RG-2). We also tested these nanoparticles for magnetic hyperthermia treatment of tumor in vitro on two tumor cell lines GL-261 and RG-2 under the application of an alternating magnetic field. Heating, efficacy and internalization properties were then evaluated. Results: Nanoparticles coated with chitosan, polyethyleneimine and neridronate are apyrogen, biocompatible and stable in aqueous suspension. The presence of a thin coating in M-Chi and M-PEI favors an arrangement in chains of the Magnetosomes, similar to that observed in Magnetosomes directly extracted from magnetotactic bacteria, while the thick matrix embedding M-Neri leads to structures with an average thickness of 3.5 µm2 per Magnetosome mineral. In the presence of GL-261 cells and upon the application of an alternating magnetic field, M-PEI and M-Chi lead to the highest specific absorption rates of 120–125 W/gFe. Furthermore, while M-Chi lead to rather low rates of cellular internalization, M-PEI strongly associate to cells, a property modulated by the application of an alternating magnetic field. Conclusions:Coating of purified Magnetosome minerals can therefore be chosen to control the interactions of nanoparticles with cells, organization of the minerals, as well as heating and cytotoxicity properties, which are important parameters to be considered in the design of a magnetic hyperthermia treatment of tumor
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The effect of iron-chelating agents on Magnetospirillum magneticum strain AMB-1: stimulated growth and Magnetosome production and improved Magnetosome heating properties
Applied Microbiology and Biotechnology, 2012Co-Authors: Edouard Alphandéry, François Guyot, Matthieu Amor, Imène ChebbiAbstract:The introduction of various iron-chelating agents to the Magnetospirillum magneticum strain AMB-1 bacterial growth medium stimulated the growth of M. magneticum strain AMB-1 magnetotactic bacteria and enhanced the production of Magnetosomes. After 7 days of growth, the number of bacteria and the production of Magnetosomes were increased in the presence of iron-chelating agents by factors of up to ∼2 and ∼6, respectively. The presence of iron-chelating agents also produced an increase in Magnetosome size and chain length and yielded improved Magnetosome heating properties. The specific absorption rate of suspensions of Magnetosome chains isolated from M. magneticum strain AMB-1 magnetotactic bacteria, measured under the application of an alternating magnetic field of average field strength ∼20 mT and frequency 198 kHz, increased from ∼222 W/g_Fe in the absence of iron-chelating agent up to ∼444 W/g_Fe in the presence of 4 μM rhodamine B and to ∼723 W/g_Fe in the presence of 4 μM EDTA. These observations were made at an iron concentration of 20 μM and iron-chelating agent concentrations below 40 μM.
François Guyot - One of the best experts on this subject based on the ideXlab platform.
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A Method for Producing Highly Pure Magnetosomes in Large Quantity for Medical Applications Using Magnetospirillum gryphiswaldense MSR-1 Magnetotactic Bacteria Amplified in Minimal Growth Media
Frontiers in Bioengineering and Biotechnology, 2020Co-Authors: Clément Berny, François Guyot, Raphael Le Fèvre, Karine Blondeau, Christine Guizonne, Emilie Rousseau, Nicolas Bayan, Edouard AlphandéryAbstract:We report the synthesis in large quantity of highly pure Magnetosomes for medical applications. For that, Magnetosomes are produced by MSR-1 Magnetospirillum gryphiswaldense magnetotactic bacteria using minimal growth media devoid of uncharacterized and toxic products prohibited by pharmaceutical regulation, i.e., yeast extract, heavy metals different from iron, and carcinogenic, mutagenic and reprotoxic agents. This method follows two steps, during which bacteria are first pre-amplified without producing Magnetosomes and are then fed with an iron source to synthesize Magnetosomes, yielding, after 50 h of growth, an equivalent OD565 of ~8 and 10 mg of Magnetosomes in iron per liter of growth media. Compared with Magnetosomes produced in non-minimal growth media, those particles have lower concentrations in metals other than iron. Very significant reduction or disappearance in Magnetosome composition of zinc, manganese, barium, and aluminum are observed. This new synthesis method paves the way towards the production of Magnetosomes for medical applications.
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biodegraded Magnetosomes with reduced size and heating power maintain a persistent activity against intracranial u87 luc mouse gbm tumors
Journal of Nanobiotechnology, 2019Co-Authors: Edouard Alphandéry, François Guyot, Ahmed Idbaih, Clovis Adam, Jean-yves Delattre, Charlotte Schmitt, Florence Gazeau, Imène ChebbiAbstract:An important but rarely addressed question in nano-therapy is to know whether bio-degraded nanoparticles with reduced sizes and weakened heating power are able to maintain sufficient anti-tumor activity to fully eradicate a tumor, hence preventing tumor re-growth. To answer it, we studied Magnetosomes, which are nanoparticles synthesized by magnetotactic bacteria with sufficiently large sizes (~ 30 nm on average) to enable a follow-up of nanoparticle sizes/heating power variations under two different altering conditions that do not prevent anti-tumor activity, i.e. in vitro cellular internalization and in vivo intra-tumor stay for more than 30 days. When Magnetosomes are internalized in U87-Luc cells by being incubated with these cells during 24 h in vitro, the dominant Magnetosome sizes within the Magnetosome size distribution (DMS) and specific absorption rate (SAR) strongly decrease from DMS ~ 40 nm and SAR ~ 1234 W/gFe before internalization to DMS ~ 11 nm and SAR ~ 57 W/gFe after internalization, a behavior that does not prevent internalized Magnetosomes to efficiently destroy U87-Luc cell, i.e. the percentage of U87-Luc living cells incubated with Magnetosomes decreases by 25% between before and after alternating magnetic field (AMF) application. When 2 µl of a suspension containing 40 µg of Magnetosomes are administered to intracranial U87-Luc tumors of 2 mm3 and exposed (or not) to 15 magnetic sessions (MS), each one consisting in 30 min application of an AMF of 27 mT and 198 kHz, DMS and SAR decrease between before and after the 15 MS from ~ 40 nm and ~ 4 W/gFe down to ~ 29 nm and ~ 0 W/gFe. Although the Magnetosome heating power is weakened in vivo, i.e. no measurable tumor temperature increase is observed after the sixth MS, anti-tumor activity remains persistent up to the 15th MS, resulting in full tumor disappearance among 50% of treated mice. Here, we report sustained Magnetosome anti-tumor activity under conditions of significant Magnetosome size reduction and complete loss of Magnetosome heating power.
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Biodegraded Magnetosomes with reduced size and heating power maintain a persistent activity against intracranial U87-Luc mouse GBM tumors
Journal of Nanobiotechnology, 2019Co-Authors: Edouard Alphandéry, François Guyot, Ahmed Idbaih, Clovis Adam, Jean-yves Delattre, Charlotte Schmitt, Florence Gazeau, Imène ChebbiAbstract:BACKGROUND: An important but rarely addressed question in nano-therapy is to know whether bio-degraded nanoparticles with reduced sizes and weakened heating power are able to maintain sufficient anti-tumor activity to fully eradicate a tumor, hence preventing tumor re-growth. To answer it, we studied Magnetosomes, which are nanoparticles synthesized by magnetotactic bacteria with sufficiently large sizes (~ 30 nm on average) to enable a follow-up of nanoparticle sizes/heating power variations under two different altering conditions that do not prevent anti-tumor activity, i.e. in vitro cellular internalization and in vivo intra-tumor stay for more than 30 days. RESULTS: When Magnetosomes are internalized in U87-Luc cells by being incubated with these cells during 24 h in vitro, the dominant Magnetosome sizes within the Magnetosome size distribution (DMS) and specific absorption rate (SAR) strongly decrease from DMS ~ 40 nm and SAR ~ 1234 W/gFe before internalization to DMS ~ 11 nm and SAR ~ 57 W/gFe after internalization, a behavior that does not prevent internalized Magnetosomes to efficiently destroy U87-Luc cell, i.e. the percentage of U87-Luc living cells incubated with Magnetosomes decreases by 25% between before and after alternating magnetic field (AMF) application. When 2 µl of a suspension containing 40 µg of Magnetosomes are administered to intracranial U87-Luc tumors of 2 mm3 and exposed (or not) to 15 magnetic sessions (MS), each one consisting in 30 min application of an AMF of 27 mT and 198 kHz, DMS and SAR decrease between before and after the 15 MS from ~ 40 nm and ~ 4 W/gFe down to ~ 29 nm and ~ 0 W/gFe. Although the Magnetosome heating power is weakened in vivo, i.e. no measurable tumor temperature increase is observed after the sixth MS, anti-tumor activity remains persistent up to the 15th MS, resulting in full tumor disappearance among 50% of treated mice. CONCLUSION: Here, we report sustained Magnetosome anti-tumor activity under conditions of significant Magnetosome size reduction and complete loss of Magnetosome heating power.
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Magnetic-field induced rotation of Magnetosome chains in silicified magnetotactic bacteria
Scientific Reports, 2018Co-Authors: Marine Blondeau, Yohan Guyodo, François Guyot, Christophe Gatel, Nicolas Menguy, Imène Chebbi, Bernard Haye, Mickaël Durand-dubief, Edouard Alphandéry, Roberta BraynerAbstract:Understanding the biological processes enabling magnetotactic bacteria to maintain oriented chains of magnetic iron-bearing nanoparticles called Magnetosomes is a major challenge. The study aimed to constrain the role of an external applied magnetic field on the alignment of Magnetosome chains in Magnetospirillum magneticum AMB-1 magnetotactic bacteria immobilized within a hydrated silica matrix. A deviation of the chain orientation was evidenced, without significant impact on cell viability, which was preserved after the field was turned-off. Transmission electron microscopy showed that the crystallographic orientation of the nanoparticles within the chains were preserved. Off-axis electron holography evidenced that the change in Magnetosome orientation was accompanied by a shift from parallel to anti-parallel interactions between individual nanocrystals. The field-induced destructuration of the chain occurs according to two possible mechanisms: (i) each Magnetosome responds individually and reorients in the magnetic field direction and/or (ii) short Magnetosome chains deviate in the magnetic field direction. This work enlightens the strong dynamic character of the Magnetosome assembly and widens the potentialities of magnetotactic bacteria in bionanotechnology. Since their discovery more than 30 years ago, magnetotactic bacteria have received much attention in the fields of geological, chemical, physical and biological sciences 1-5. However, the processes by which they synthesize iron oxide (or sulphide) magnetic nanoparticles and organize them into chains allowing the cell to orient itself along the geomagnetic field are still far from being fully understood 6-10. It is well-admitted that production of the nano-crystals occurs in specialized organelles, called Magnetosomes, formed by a membrane invagination at multiple sites in the cell. However, identifying the proteins controlling nucleation, size, shape and arrangement in chains of the nanocrystals, as well as the mechanisms of action of these proteins, remains a challenging task 11-15. Phenotypic divergences between different species were evidenced 16. In some Magnetospirillum sp. strains, the chain is stabilized along the longitudinal axis of the cell by an organic filament, MamK protein, while the connection of Magnetosomes to this structure is provided by a protein MamJ 17,18. The deletion of MamK gene in Magnetospirillum gryphiswaldense MSR-1 leads to short chains separated by gaps devoid of Magnetosomes, while the deletion of MamJ induces aggregation of Magnetosomes within the cell with observable filaments not attached to the biogenic particles 19,20. In Magnetospirillum magneticum AMB-1, additional MamJ-like and MamK-like proteins were identified that are involved in the dynamic of the filament and the Magnetosome organization in chain 21-23. The capacity of the Magnetosome chain to act as a compass is not only related to the spatial arrangement of nanocrystals, but also to their crystallographic and magnetic alignment. In some magnetotactic bacteria (e.g., Magnetospirillum sp.), the biogenic magnetite nanoparticles have a cubo-octahedral morphology with a magnetic
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Biocompatible coated Magnetosome minerals with various organization and cellular interaction properties induce cytotoxicity towards RG-2 and GL-261 glioma cells in the presence of an alternating magnetic field
Journal of Nanobiotechnology, 2017Co-Authors: Yasmina Hamdous, François Guyot, Imène Chebbi, Chalani Mandawala, Raphael Le Fèvre, Olivier Seksek, Edouard AlphandéryAbstract:Background: Biologics magnetics nanoparticles, Magnetosomes, attract attention because of their magnetic characteristics and potential applications. The aim of the present study was to develop and characterize novel Magnetosomes, which were extracted from magnetotactic bacteria, purified to produce apyrogen Magnetosome minerals, and then coated with Chitosan, Neridronate, or Polyethyleneimine. It yielded stable Magnetosomes designated as M-Chi, M-Neri, and M-PEI, respectively. Nanoparticle biocompatibility was evaluated on mouse fibroblast cells (3T3), mouse glioblastoma cells (GL-261) and rat glioblastoma cells (RG-2). We also tested these nanoparticles for magnetic hyperthermia treatment of tumor in vitro on two tumor cell lines GL-261 and RG-2 under the application of an alternating magnetic field. Heating, efficacy and internalization properties were then evaluated. Results: Nanoparticles coated with chitosan, polyethyleneimine and neridronate are apyrogen, biocompatible and stable in aqueous suspension. The presence of a thin coating in M-Chi and M-PEI favors an arrangement in chains of the Magnetosomes, similar to that observed in Magnetosomes directly extracted from magnetotactic bacteria, while the thick matrix embedding M-Neri leads to structures with an average thickness of 3.5 µm2 per Magnetosome mineral. In the presence of GL-261 cells and upon the application of an alternating magnetic field, M-PEI and M-Chi lead to the highest specific absorption rates of 120–125 W/gFe. Furthermore, while M-Chi lead to rather low rates of cellular internalization, M-PEI strongly associate to cells, a property modulated by the application of an alternating magnetic field. Conclusions:Coating of purified Magnetosome minerals can therefore be chosen to control the interactions of nanoparticles with cells, organization of the minerals, as well as heating and cytotoxicity properties, which are important parameters to be considered in the design of a magnetic hyperthermia treatment of tumor
Wei Jiang - One of the best experts on this subject based on the ideXlab platform.
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Improved methods for mass production of Magnetosomes and applications: a review.
Microbial cell factories, 2020Co-Authors: Abdul Basit, Jiaojiao Wang, Fangfang Guo, Wei Niu, Wei JiangAbstract:Magnetotactic bacteria have the unique ability to synthesize Magnetosomes (nano-sized magnetite or greigite crystals arranged in chain-like structures) in a variety of shapes and sizes. The chain alignment of Magnetosomes enables magnetotactic bacteria to sense and orient themselves along geomagnetic fields. There is steadily increasing demand for Magnetosomes in the areas of biotechnology, biomedicine, and environmental protection. Practical difficulties in cultivating magnetotactic bacteria and achieving consistent, high-yield Magnetosome production under artificial environmental conditions have presented an obstacle to successful development of Magnetosome applications in commercial areas. Here, we review information on Magnetosome biosynthesis and strategies for enhancement of bacterial cell growth and Magnetosome formation, and implications for improvement of Magnetosome yield on a laboratory scale and mass-production (commercial or industrial) scale.
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the disruption of an oxyr like protein impairs intracellular magnetite biomineralization in magnetospirillum gryphiswaldense msr 1
Frontiers in Microbiology, 2017Co-Authors: Yunpeng Zhang, Fangfang Guo, Jiesheng Tian, Tong Wen, Yuanyuan Geng, Junquan Liu, Tao Peng, Guohua Guan, Wei JiangAbstract:Magnetotactic bacteria (MTB) synthesize intracellular membrane-enveloped magnetite bodies known as Magnetosomes which have been applied in biotechnology and medicine. A series of proteins involved in ferric ion transport and redox required for magnetite formation have been identified but the knowledge of Magnetosome biomineralization remains very limited. Here, we identify a novel OxyR homolog (named OxyR-Like), the disruption of which resulted in low ferromagnetism and disfigured nano-sized iron oxide crystals. High resolution-transmission electron microscopy (HRTEM) showed that these nanoparticles are mainly composed of magnetite accompanied with ferric oxide including α-Fe2O3 and e-Fe2O3. Electrophoretic mobility shift assay (EMSA) and DNase I footprinting showed that OxyR-Like binds the conserved 5’-GATA-N{9}-TATC-3’ region within the promoter of pyruvate dehydrogenase (pdh) complex operon. Quantitative real-time reverse transcriptase PCR indicated that not only the expression of pdh operon but also genes related to Magnetosomes biosynthesis and tricarboxylic acid cycle decreased dramatically, suggesting a link between carbon metabolism and Magnetosome formation. Taken together, our results show that OxyR-Like plays a key role in Magnetosomes formation.
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a novel role for crp in controlling Magnetosome biosynthesis in magnetospirillum gryphiswaldense msr 1
Scientific Reports, 2016Co-Authors: Tong Wen, Fangfang Guo, Jiesheng Tian, Yunpeng Zhang, Wei JiangAbstract:Magnetotactic bacteria (MTB) are specialized microorganisms that synthesize intracellular magnetite particles called Magnetosomes. Although many studies have focused on the mechanism of Magnetosome synthesis, it remains unclear how these structures are formed. Recent reports have suggested that Magnetosome formation is energy dependent. To investigate the relationship between Magnetosome formation and energy metabolism, a global regulator, named Crp, which mainly controls energy and carbon metabolism in most microorganisms, was genetically disrupted in Magnetospirillum gryphiswaldense MSR-1. Compared with the wild-type or complemented strains, the growth, ferromagnetism and intracellular iron content of crp-deficient mutant cells were dramatically decreased. Transmission electron microscopy (TEM) showed that Magnetosome synthesis was strongly impaired by the disruption of crp. Further gene expression profile analysis showed that the disruption of crp not only influenced genes related to energy and carbon metabolism, but a series of crucial Magnetosome island (MAI) genes were also down regulated. These results indicate that Crp is essential for Magnetosome formation in MSR-1. This is the first time to demonstrate that Crp plays an important role in controlling Magnetosome biomineralization and provides reliable expression profile data that elucidate the mechanism of Crp regulation of Magnetosome formation in MSR-1.
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Surface expression of protein A on Magnetosomes and capture of pathogenic bacteria by Magnetosome/antibody complexes.
Frontiers in microbiology, 2014Co-Authors: Lingzi Liu, Wei Jiang, Xu Wang, Zhang Huiyuan, Jiesheng TianAbstract:Magnetosomes are membrane-enclosed magnetite nanocrystals synthesized by magnetotactic bacteria (MTB). They display chemical purity, narrow size ranges, and species-specific crystal morphologies. Specific transmembrane proteins are sorted to the Magnetosome membrane (MM). MamC is the most abundant MM protein of Magnetospirillum gryphiswaldense strain MSR-1. MamF is the second most abundant MM protein of MSR-1 and forms stable oligomers. We expressed staphylococcal protein A (SPA), an immunoglobulin-binding protein from the cell wall of Staphylococcus aureus, on MSR-1 Magnetosomes by fusion with MamC or MamF. The resulting recombinant Magnetosomes were capable of self-assembly with the Fc region of mammalian antibodies (Abs) and were therefore useful for functionalization of Magnetosomes. Recombinant plasmids pBBR-mamC-spa and pBBR-mamF-spa were constructed by fusing spa (the gene that encodes SPA) with mamC and mamF, respectively. Recombinant Magnetosomes with surface expression of SPA were generated by introduction of these fusion genes into wild-type MSR-1 or a mamF mutant strain. Studies with a Zeta Potential Analyzer showed that the recombinant Magnetosomes had hydrated radii significantly smaller than those of WT Magnetosomes and zeta potentials less than -30 mV, indicating that the Magnetosome colloids were relatively stable. Observed conjugation efficiencies were as high as 71.24 µg Ab per mg recombinant Magnetosomes, and the conjugated Abs retained most of their activity. Numbers of Vibrio parahaemolyticus (a common pathogenic bacterium in seafood) captured by recombinant Magnetosome/ Ab complexes were measured by real-time fluorescence-based quantitative PCR. One mg of complex was capable of capturing as many as 1.74×107 Vibrio cells. The surface expression system described here will be useful for design of functionalized Magnetosomes from MSR-1 and other MTB.
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surface expression of protein a on Magnetosomes and capture of pathogenic bacteria by Magnetosome antibody complexes
Frontiers in Microbiology, 2014Co-Authors: Lingzi Liu, Wei Jiang, Xu Wang, Huiyuan Zhang, Jiesheng TianAbstract:Magnetosomes are membrane-enclosed magnetite nanocrystals synthesized by magnetotactic bacteria (MTB). They display chemical purity, narrow size ranges, and species-specific crystal morphologies. Specific transmembrane proteins are sorted to the Magnetosome membrane (MM). MamC is the most abundant MM protein of Magnetospirillum gryphiswaldense strain MSR-1. MamF is the second most abundant MM protein of MSR-1 and forms stable oligomers. We expressed staphylococcal protein A (SPA), an immunoglobulin-binding protein from the cell wall of Staphylococcus aureus, on MSR-1 Magnetosomes by fusion with MamC or MamF. The resulting recombinant Magnetosomes were capable of self-assembly with the Fc region of mammalian antibodies (Abs) and were therefore useful for functionalization of Magnetosomes. Recombinant plasmids pBBR-mamC-spa and pBBR-mamF-spa were constructed by fusing spa (the gene that encodes SPA) with mamC and mamF, respectively. Recombinant Magnetosomes with surface expression of SPA were generated by introduction of these fusion genes into wild-type MSR-1 or a mamF mutant strain. Studies with a Zeta Potential Analyzer showed that the recombinant Magnetosomes had hydrated radii significantly smaller than those of WT Magnetosomes and zeta potentials less than -30 mV, indicating that the Magnetosome colloids were relatively stable. Observed conjugation efficiencies were as high as 71.24 µg Ab per mg recombinant Magnetosomes, and the conjugated Abs retained most of their activity. Numbers of Vibrio parahaemolyticus (a common pathogenic bacterium in seafood) captured by recombinant Magnetosome/ Ab complexes were measured by real-time fluorescence-based quantitative PCR. One mg of complex was capable of capturing as many as 1.74×107 Vibrio cells. The surface expression system described here will be useful for design of functionalized Magnetosomes from MSR-1 and other MTB.
