Hybrid biorobot
The erythrocyte and the bacterium have been turned into a tool for targeted drug delivery
Grigory Kopiev, N+1
German scientists have constructed a substance deliverer inside the body from red blood cells and E. coli. A bacterium with flagella attaches to an erythrocyte carrying a drug or other substance, as well as superparamagnetic nanoparticles. As a result, a structure is formed in which the bacterium is responsible for moving forward, and the erythrocyte corrects the direction under the influence of an external magnetic field, researchers report in the journal Science Robotics (Alapan et al., Soft erythrocyte-based bacterial microswimmers for cargo delivery).
Almost all medications have side effects. This is often due to the fact that the active substance gets not only into the right organ, but also into other areas of the body. To solve this problem, scientists are creating systems of "targeted" drug delivery. So that the delivery vehicles themselves do not cause harm, they are often made not artificial, but from living cells or microorganisms. But in this case it is quite difficult to create an effective and accurate system of movement and control.
Scientists led by Metin Sitti from the Institute of Intelligent Systems of the Max Planck Society have created a new complex for point delivery of substances based on two biological objects — erythrocyte cells and a strain of Escherichia coli (Escherichia coli MG1655) bacteria with flagella. As a delivery agent, the researchers chose doxorubicin, which is often used in cancer chemotherapy.
First, the researchers placed red blood cells in a solution containing doxorubicin, superparamagnetic iron oxide nanoparticles, as well as auxiliary substances. The processing conditions and the concentration of substances were selected in such a way that pores opened in the erythrocytes, through which hemoglobin left them and doxorubicin and iron oxide particles penetrated, and then the pores closed again. As a result, a cell appeared that carried the right substance and was suitable for control using a magnetic field. However, it cannot move by itself, so scientists attached an E. coli bacterium with flagella to it as a motor.
To securely attach the bacterium to the erythrocyte, scientists genetically modified it so that it expresses a protein labeled with biotin on its membrane. These bacteria were also coated with streptavidin, which forms one of the strongest non-covalent bonds in nature with biotin. Since the erythrocytes were also coated with biotin, they reliably connected with bacteria and formed a single structure in which the bacterium acts as an engine, and the erythrocyte serves as a "steering wheel".
The structure of the resulting ligament from bacteria and erythrocyte
(drawings from an article in Science Robotics)
The researchers experimentally tested the operability of such a scheme by using five electromagnetic coils that allowed changing the magnetic induction vector and rotating the entire complex. The researchers note that some of the samples moved in a relatively straight line, and the other part in a spiral. The authors attribute this to the fact that some of the bacteria could attach to the erythrocyte from the side, and not in the center.
Movement of the complex in an external magnetic field
Scientists have tested the mechanism of release of the substance from the erythrocyte. It turned out that at a pH of 3.1, 98 percent of doxorubicin leaves the erythrocyte per day. Researchers suggest using this property to deliver this or other substances to cancerous tumors for which the acidic environment is considered favorable. In addition to the mechanism of drug release, scientists have provided a mechanism for killing red blood cells and bacteria after performing the work. To do this, they injected into red blood cells a substance that is strongly heated by radiation in the near infrared range and causes the death of bacteria and red blood cells from overheating.
There are many other developments for point-to-point drug delivery based on biological objects. For example, last year another group of scientists from Germany created a hybrid deliverer of doxorubicin to cancer cells, consisting of a sperm and a metal structure. It allows you to control the movement of the sperm using a magnetic field, as well as release the substance when it collides with tumor cells.
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