Abstract
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.
Highlights
Iron oxide nanoparticles (IONP) offer a series of appealing properties, such as their faculty to enhance contrast in magnetic resonance imaging (Choi et al, 2004), to efficiently carry drugs (Jain et al, 2005), or to produce localized heat for tumor hyperthermia treatments under the application of an alternating magnetic field or laser (Beik et al, 2016)
We removed from the three media all constituents that are not compatible with medical regulation (YE, heavy metals apart from iron, and CMR agents) and we determined the lowest concentration of remaining chemicals that enables bacterial growth and magnetosome production to yield “highly pure magnetosomes.”
To assess bacterial growth and magnetosome production, we grew bacteria in 50 mL tubes (See “Material and Method”) and measured at D6 and D13, the properties of the bacteria contained in these tubes, i.e., the optical density at 565 nm (OD565) as well as the magnetic response (MR) of the bacterial suspensions, which is the percentage of bacteria that orientates parallel to a magnetic field applied by a magnet as observed by optical microscopy
Summary
Iron oxide nanoparticles (IONP) offer a series of appealing properties, such as their faculty to enhance contrast in magnetic resonance imaging (Choi et al, 2004), to efficiently carry drugs (Jain et al, 2005), or to produce localized heat for tumor hyperthermia treatments under the application of an alternating magnetic field or laser (Beik et al, 2016). MSR-1 magnetites display an organization in chains that prevents their aggregation (Heyen and Schüler, 2003), have high crystallinity, homogenous size distribution and improved heating properties in comparison to chemically synthesized IONP (Hamdous et al, 2017; Mandawala et al, 2017) These biological nanoparticles have been considered for various medical applications, especially for tumor nanoparticle-mediated hyperthermia treatments (Alphandéry et al, 2017; Le Fèvre et al, 2017).
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