Abstract
We report the fabrication of highly pure magnetosomes that are synthesized by magnetotactic bacteria (MTB) using pharmaceutically compatible growth media, i.e., without compounds of animal origin (yeast extracts), carcinogenic, mutagenic, or toxic for reproduction (CMR) products, and other heavy metals than iron. To enable magnetosome medical applications, these growth media are reduced and amended compared with media commonly used to grow these bacteria. Furthermore, magnetosomes are made non-pyrogenic by being extracted from these micro-organisms and heated above 400 °C to remove and denature bacterial organic material and produce inorganic magnetosome minerals. To be stabilized, these minerals are further coated with citric acid to yield M-CA, leading to fully reconstructed chains of magnetosomes. The heating properties and anti-tumor activity of highly pure M-CA are then studied by bringing M-CA into contact with PC3-Luc tumor cells and by exposing such assembly to an alternating magnetic field (AMF) of 42 mT and 195 kHz during 30 min. While in the absence of AMF, M-CA are observed to be non-cytotoxic, they result in a 35% decrease in cell viability following AMF application. The treatment efficacy can be associated with a specific absorption rate (SAR) value of M-CA, which is relatively high in cellular environment, i.e., SARcell = 253 ± 11 W/gFe, while being lower than the M-CA SAR value measured in water, i.e., SARwater = 1025 ± 194 W/gFe, highlighting that a reduction in the Brownian contribution to the SAR value in cellular environment does not prevent efficient tumor cell destruction with these nanoparticles.
Key points
• Highly pure magnetosomes were produced in pharmaceutically compatible growth media
• Non-pyrogenic and stable magnetosomes were prepared for human injection
• Magnetosomes efficiently destroyed prostate tumor cells in magnetic hyperthermia
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Acknowledgements
We would like to thank the BPI (“banque publique d’investissement, France”), the region of Paris (“Paris Région Entreprise, France”), the French Research Tax Credit program (“crédit d’impôt recherche”), the incubator Paris Biotech Santé, the ANRT (CIFRE 2014/0359, CIFRE 2016/0747, CIFRE 2013/0364, CIFRE 2015/976), the Eurostars programs (Nanoneck-2 E9309 and Nanoglioma E11778), the AIR program (“aide à l’innovation responsible”) from the region of Paris (A1401025Q), the ANR (“Agence Nationale de la Recherche”) Méfisto, as well as the Universities Paris 6 and Paris 11. We also would like to thank the Nomis Foundation and Markus Reinhard for their support.
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TN, IC, and RL contributed to the study conception, design, and data analysis. TN carried out the experiments and collected the data. TN wrote the first version of the manuscript taking into consideration some advice given by IC and FG. EA reviewed and edited the first version of the manuscript. FG participated significantly in the acquisition of transmission electron microscopy data, in the analysis of all the results, and in the writing of the article. TN is a PhD student who has carried out her PhD under the supervision of EA and FG. All the authors commented on previous versions of the manuscript. All the authors read and approved the final manuscript.
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Nguyen, T.N., Chebbi, I., Le Fèvre, R. et al. Non-pyrogenic highly pure magnetosomes for efficient hyperthermia treatment of prostate cancer. Appl Microbiol Biotechnol 107, 1159–1176 (2023). https://doi.org/10.1007/s00253-022-12247-9
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DOI: https://doi.org/10.1007/s00253-022-12247-9