Friday, September 23, 2016

Magneto-Aerotactic Bacteria Deliver Drug-Containing Nanoliposomes to Tumour Hypoxic Regions

In Chapter 8 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I describe magnetotactic bacteria.
Several species of bacteria contain linear strings of up to 20 particles of magnetite, each about 50 nm on a side encased in a membrane (Frankelet al. 1979; Moskowitz 1995). Over a dozen different bacteria have been identified that synthesize these intracellular, membrane-bound particles or magnetosomes (Fig. 8.25). In the laboratory the bacteria align themselves with the local magnetic field. In the problems you will learn that there is sufficient magnetic material in each bacterium to align it with the earth’s field just like a compass needle. Because of the tilt of the earth’s field, bacteria in the wild can thereby distinguish up from down.

Other bacteria that live in oxygen-poor, sulfide-rich environments contain magnetosomes composed of greigite (Fe3S4), rather than magnetite (Fe3O4). In aquatic habitats, high concentrations of both kinds of magnetotactic bacteria are usually found near the oxic–anoxic transition zone (OATZ). In freshwater environments the OATZ is usually at the sediment–water interface. In marine environments it is displaced up into the water column. Since some bacteria prefer more oxygen and others prefer less, and they both have the same kind of propulsion and orientation mechanism, one wonders why one kind of bacterium is not swimming out of the environment favorable to it. Frankel and Bazylinski(1994) proposed that the magnetic field and the magnetosomes keep the organism aligned with the field, and that they change the direction in which their flagellum rotates to move in the direction that leads them to a more favorable concentration of some desired chemical.
I enjoy learning about the biology and physics of magnetotactic bacteria, but I never expected that they had anything to do with medicine. Then last month a paper published in Nature Nanotechnology discussed using these bacteria to treat cancer!
Oxygen-depleted hypoxic regions in the tumour are generally resistant to therapies. Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour of magnetotactic bacteria, Magnetococcus marinus strain MC-1 (ref. 4), can be used to transport drug-loaded nanoliposomes into hypoxic regions of the tumour. In their natural environment, MC-1 cells, each containing a chain of magnetic iron-oxide nanocrystals, tend to swim along local magnetic field lines and towards low oxygen concentrations based on a two-state aerotactic sensing system. We show that when MC-1 cells bearing covalently bound drug-containing nanoliposomes were injected near the tumour in severe combined immunodeficient beige mice and magnetically guided, up to 55% of MC-1 cells penetrated into hypoxic regions of HCT116 colorectal xenografts. Approximately 70 drug-loaded nanoliposomes were attached to each MC-1 cell. Our results suggest that harnessing swarms of microorganisms exhibiting magneto-aerotactic behaviour can significantly improve the therapeutic index of various nanocarriers in tumour hypoxic regions.
The IOP website published an article by Belle Dumé describing this study. It begins
Bacteria that respond to magnetic fields and low oxygen levels may soon join the fight against cancer. Researchers in Canada have done experiments that show how magneto-aerotactic bacteria can be used to deliver drugs to hard-to-reach parts of tumours. With further development, the method could be used to treat a variety of solid tumours, which account for roughly 85% of all cancers.
A similar article, also by Dumé, can be found on
As cancer cells proliferate, they consume large amounts of oxygen. This results in oxygen-poor regions in a tumour. It is notoriously difficult to treat these hypoxic regions using conventional pharmaceutical nanocarriers, such as liposomes, micelles and polymeric nanoparticles.

Now, a team led by Sylvain Martel of the NanoRobotics Laboratory at the Polytechnique Montréal has developed a method that exploits the magnetotactic bacteria Magnetoccus marinus (MC-1) to overcome this problem.
Pretty cool stuff.

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