Unlocking the Potential of Magnetotactic Bacteria as Magnetic Hyperthermia Agents.

Magnetotactic bacteria are aquatic microorganisms that internally biomineralize chains of magnetic nanoparticles (called magnetosomes) and use them as a compass. Here it is shown that magnetotactic bacteria of the strain Magnetospirillum gryphiswaldense present high potential as magnetic hyperthermia agents for cancer treatment. Their heating efficiency or specific absorption rate is determined using both calorimetric and AC magnetometry methods at different magnetic field amplitudes and frequencies. In addition, the effect of the alignment of the bacteria in the direction of the field during the hyperthermia experiments is also investigated. The experimental results demonstrate that the biological structure of the magnetosome chain of magnetotactic bacteria is perfect to enhance the hyperthermia efficiency. Furthermore, fluorescence and electron microscopy images show that these bacteria can be internalized by human lung carcinoma cells A549, and cytotoxicity studies reveal that they do not affect the viability or growth of the cancer cells. A preliminary in vitro hyperthermia study, working on clinical conditions, reveals that cancer cell proliferation is strongly affected by the hyperthermia treatment, making these bacteria promising candidates for biomedical applications.

An Investigation of the Sensing Capabilities of Magnetotactic Bacteria.

We investigate the sensing capabilities of magnetotactic bacteria (Magnetospirillum gryphiswaldense strain MSR1) to MCF-7 breast cancer cells. Cancer cells are allowed to grow inside a capillary tube with depth of 200 $\mu \mathrm {m}$ and motion of magnetotactic bacteria is investigated under the influence of oxygen gradient and geomagnetic field. The influence of cancer cells is modeled to predict the oxygen gradient within the capillary tube in three-dimensional space. Our experimental motion analysis and count of motile magnetotactic bacteria indicate that they migrate towards less-oxygenated regions within the vicinity of cancer cells. Bands of magnetotactic bacteria with average concentration of 18.8±2.0% are observed in close proximity to MCF-7 cells $(h = 20~ \mu \mathrm {m})$, whereas the concentration at proximity of $190~ \mu \mathrm {m}$ is 5.0 ± 6.8%.

Physiological characteristics of Magnetospirillum gryphiswaldense MSR-1 that control cell growth under high-iron and low-oxygen conditions.

Magnetosome formation by Magnetospirillum gryphiswaldense MSR-1 is dependent on iron and oxygen levels. We used transcriptome to evaluate transcriptional profiles of magnetic and non-magnetic MSR-1 cells cultured under high-iron and low-iron conditions. A total of 80 differentially expressed genes (DEGs) were identified, including 53 upregulated and 27 downregulated under high-iron condition. These DEGs belonged to the functional categories of biological regulation, oxidation-reduction process, and ion binding and transport, and were involved in sulfur metabolism and cysteine/methionine metabolism. Comparison with our previous results from transcriptome data under oxygen-controlled conditions indicated that transcription of mam or mms was not regulated by oxygen or iron signals. 17 common DEGs in iron- and oxygen-transcriptomes were involved in energy production, iron transport, and iron metabolism. Some unknown-function DEGs participate in iron transport and metabolism, and some are potential biomarkers for identification of Magnetospirillum strains. IrrA and IrrB regulate iron transport in response to low-oxygen and high-iron signals, respectively. Six transcription factors were predicted to regulate DEGs. Fur and Crp particularly co-regulate DEGs in response to changes in iron or oxygen levels, in a proposed joint regulatory network of DEGs. Our findings provide new insights into biomineralization processes under high- vs. low-iron conditions in magnetotactic bacteria.

A New Magnetotactic Bacteria Optimization Algorithm Based on Moment Migration.

Magnetotactic bacteria is a kind of polyphyletic group of prokaryotes with the characteristics of magnetotaxis that make them orient and swim along geomagnetic field lines. Its distinct biology characteristics are useful to design new optimization technology. In this paper, a new bionic optimization algorithm named Magnetotactic Bacteria Moment Migration Algorithm (MBMMA) is proposed. In the proposed algorithm, the moments of a chain of magnetosomes are considered as solutions. The moments of relative good solutions can migrate each other to enhance the diversity of the MBMMA. It is compared with variants of PSO on standard functions problems. The experiment results show that the MBMMA is effective in solving optimization problems. It shows better or competitive performance compared with the variants of PSO on most of the tested functions in this paper.

Biosynthesis of magnetic nanoparticles by human mesenchymal stem cells following transfection with the magnetotactic bacterial gene mms6.

The use of stem cells to support tissue repair is facilitated by loading of the therapeutic cells with magnetic nanoparticles (MNPs) enabling magnetic tracking and targeting. Current methods for magnetizing cells use artificial MNPs and have disadvantages of variable uptake, cellular cytotoxicity and loss of nanoparticles on cell division. Here we demonstrate a transgenic approach to magnetize human mesenchymal stem cells (MSCs). MSCs are genetically modified by transfection with the mms6 gene derived from Magnetospirillum magneticum AMB-1, a magnetotactic bacterium that synthesises single-magnetic domain crystals which are incorporated into magnetosomes. Following transfection of MSCs with the mms6 gene there is bio-assimilated synthesis of intracytoplasmic magnetic nanoparticles which can be imaged by MR and which have no deleterious effects on cell proliferation, migration or differentiation. The assimilation of magnetic nanoparticle synthesis into mammalian cells creates a real and compelling, cytocompatible, alternative to exogenous administration of MNPs.

Cytotoxicity and genotoxicity of bacterial magnetosomes against human retinal pigment epithelium cells.

A variety of nanomaterials have been developed for ocular diseases. The ability of these nanomaterials to pass through the blood-ocular barrier and their biocompatibility are essential characteristics that must be considered. Bacterial magnetosomes (BMs) are a type of biogenic magnetic nanomaterials synthesized by magnetotactic bacteria. Due to their unique biomolecular membrane shell and narrow size distribution of approximately 30 nm, BMs can pass through the blood-brain barrier. The similarity of the blood-ocular barrier to the blood-brain barrier suggests that BMs have great potential as treatments for ocular diseases. In this work, BMs were isolated from magnetotactic bacteria and evaluated in various cytotoxicity and genotoxicity studies in human retinal pigment epithelium (ARPE-19) cells. The BMs entered ARPE-19 cells by endocytosis after a 6-h incubation and displayed much lower cytotoxicity than chemically synthesized magnetic nanoparticles (MNPs). MNPs exhibited significantly higher genotoxicity than BMs and promoted the expression of Bax (the programmed cell death acceleration protein) and the induction of greater cell necrosis. In BM-treated cells, apoptosis tended to be suppressed via increased expression of the Bcl-2 protein. In conclusion, BMs display excellent biocompatibility and potential for use in the treatment of ocular diseases.

Visualizing implanted tumors in mice with magnetic resonance imaging using magnetotactic bacteria.

PURPOSE: To determine if magnetotactic bacteria can target tumors in mice and provide positive contrast for visualization using magnetic resonance imaging. EXPERIMENTAL DESIGN: The ability of the magnetotactic bacterium, Magnetospirillum magneticum AMB-1 (referred to from here as AMB-1), to confer positive magnetic resonance imaging contrast was determined in vitro and in vivo. For the latter studies, AMB-1 were injected either i.t. or i.v. Bacterial growth conditions were manipulated to produce small (approximately 25-nm diameter) magnetite particles, which were observed using transmission electron microscopy. Tumor targeting was confirmed using 64Cu-labeled bacteria and positron emission tomography and by determination of viable cell counts recovered from different organs and the tumor. RESULTS: We show that AMB-1 bacteria with small magnetite particles generate T1-weighted positive contrast, enhancing in vivo visualization by magnetic resonance imaging. Following i.v. injection of 64Cu-labeled AMB-1, positron emission tomography imaging revealed increasing colonization of tumors and decreasing infection of organs after 4 hours. Viable cell counts showed that, by day 6, the bacteria had colonized tumors but were cleared completely from other organs. Magnetic resonance imaging showed a 1.22-fold (P = 0.003) increased positive contrast in tumors on day 2 and a 1.39-fold increase (P = 0.0007) on day 6. CONCLUSION: Magnetotactic bacteria can produce positive magnetic resonance imaging contrast and colonize mouse tumor xenografts, providing a potential tool for improved magnetic resonance imaging visualization in preclinical and translational studies to track cancer.