Microbes-oncologists

Magnetosensitive bacteria delivered the medicine to the tumor

Oleg Lischuk, N+1

Canadian scientists have developed a method of delivering drugs to hard-to-reach areas of tumors with the help of bacteria sensitive to the magnetic field and oxygen levels. The results of the work are published in the journal Nature Nanotechnology (Felfoul et al., Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions).

Fast-growing malignant neoplasms actively absorb oxygen, which is why some of their areas experience oxygen starvation (the so-called hypoxic areas). The existing nanosystems of targeted drug delivery, including liposomes, micelles and polymer nanoparticles carried by the bloodstream, cannot create sufficient concentrations of the drug in these areas.

The staff of the Montreal Polytechnic School, McGill and Montreal Universities decided to use the strain MS-1 of the bacterium Magnetococcus marinus for these purposes. Its cells contain organelles sensitive to the magnetic field — magnetosomes, which are crystals of magnetic iron oxide enclosed in a lipid membrane. In addition, these microorganisms are sensitive to the concentration of oxygen in the environment and are capable of active movement. In natural conditions, they move along the lines of the Earth's magnetic field until they find a zone with a reduced oxygen content. When they find such a zone, they migrate to where the oxygen concentration is minimal — such conditions of existence are preferable for them.

Drawing from the press release of the Polytechnique Montréal
Legions of nanorobots target cancerous tumours with precision – VM.

Scientists injected MS-1 into immunodeficient mice with colon carcinoma from implanted human cells. After that, the animals were placed in a magnetic field focused on the tumor and made sure that the bacteria were accumulating in its hypoxic areas (unlike the polymer microspheres used for control).

Accumulation of MC-1-LP in hypoxic tumor sites
Ouajdi Felfoul et al, Nature Nanotechnology, 2016

At the second stage of the experiment, the researchers loaded MS-1 with covalently bound liposomes with the antitumor drug SN-38. After the introduction of these bacteria (MS-1-LP) to mice in the tumor area, liposomes were distributed throughout its entire volume, mainly in areas of hypoxia and necrosis. The level of their targeted accumulation in the neoplasm exceeded 50 percent.

At the same time, the introduction of more than 100 million bacteria did not cause the release of cytokines (evidence of an inflammatory reaction) and did not harm the blood cells of animals. Thus, the developed technique is able to deliver drugs to hard-to-reach areas of tumors more effectively than artificial nanosystems, significantly reducing the toxic effects of drugs on other organs and tissues. At the same time, its experimental use in animals had no pronounced side effects.

According to the researchers, in the future, the effectiveness of MS-1 can be further improved by genetic modification of bacteria and improving their magnetic guidance algorithms.

As already mentioned, liposomes, micelles, polymer microspheres and other nanoconstructions are used in experiments for targeted drug delivery. All of them have disadvantages that limit their use. Various scientific collectives of the world are constantly engaged in their improvement. For example, scientists from Berkeley taught nanomycells to penetrate the brain, researchers from Barcelona proposed transporting drugs on microscopic magnetic "carpets", and an American group of scientists disguised polymer nanoparticles from the immune system by covering them with a platelet membrane. Attempts were also made to use biological objects, as in the Canadian work described: an international scientific team used modified diatoms for these purposes.

Portal "Eternal youth" http://vechnayamolodost.ru  25.08.2016