Upstream
Microspheres swam against the blood flow and delivered the drug to the cancer cells
Grigory Kopiev, N+1
Scientists from Germany, Turkey and the USA have created microspheres controlled by an external magnetic field for the point delivery of drugs through blood vessels. They are able to float along the blood stream in any direction, and when they come into contact with cancer cells, they bind to them thanks to a coating with antibodies to a protein specific to such cells. They also contain an anti-cancer drug and are able to release it after joining cancer cells under the influence of light. Article by Alapan et al. Multifunctional surface microrollers for targeted cargo delivery in physiological blood flow published in Science Robotics.
In medical research, the direction of searching for methods and substances for targeted drug delivery has long been formed. First of all, it is necessary for drugs with significant side effects. For example, for cancer chemotherapy, the drug doxorubicin has been used for a long time, which, in addition to its antitumor effect, has many side effects that affect many organs and systems of the body. One of the consequences of this is that the dose of the drug has to be limited so that the toxic effect from it does not become critical. With the help of targeted delivery of the drug directly into the tumor, this could be at least partially avoided.
One of the most promising methods is considered to be the delivery of medicines to a specific area using controlled micro robots. Scientists have already made some progress in this area, but almost all of their developments are limited in working conditions. In particular, they are unable to move arbitrarily through the vessels of the circulatory system, which is a universal binding element for various organs and can potentially act as a convenient medium for delivering micro robots to the workplace.
Metin Sitti from the Max Planck Society's Institute for Intelligent Systems and At the University, Koch and his colleagues created a micro robot (microsphere) capable of moving even against the flow of blood. It is based on a sphere of silicon oxide with a diameter of 7.8 or 3 micrometers (scientists have tested two options), one of the sides of which is covered with layers of nickel and gold, and the second with antibodies to the HER2 protein and doxorubicin bound to the particle through a substance destroyed by ultraviolet irradiation.
Scheme of creation of a microsphere with a functional surface. Figures from the article by Alapan et al.
The scientists tested the ability of microspheres to bind to cancer cells on a standard SKBR3 breast cancer cell line expressing the HER2 protein. When compared with pure microspheres without antibodies, it turned out that they do not bind to cells at all and are washed away by a liquid flow, and microspheres with antibodies bind and are retained. Then the scientists conducted a full-fledged check and after binding the microspheres to cancer cells, irradiated them with ultraviolet radiation. Thanks to the fluorescent marker substance, they were able to track that doxorubicin was released from the microspheres and entered the cells, as expected.
Diagram and pictures of microspheres, as well as a diagram of their movement through a blood vessel.
The nickel layer is necessary to control the microsphere. A rotating magnetic field is created outside, affecting the microsphere and causing it to rotate. Its orientation is such that the microsphere rotates in a plane perpendicular to the plane of the adjacent vessel wall. Under normal conditions, the microsphere would simply rotate in place, but the vessel wall located next to it makes changes in the behavior of fluid flows near it, so the side of the sphere facing the wall experiences a retarding effect. This unevenness in external influences between the two sides of the microsphere leads to the fact that its rotational motion is partially transformed into translational. And the rotation of the orientation of the rotating magnetic field allows you to change the direction of translational motion.
The forces acting on the microsphere from different sides, and the total force responsible for the translational motion.
Researchers have successfully confirmed the ability of microspheres to move in a controlled manner. They placed them in a tube with a blood stream and showed that microspheres are able to move, following a magnetic field, even in a stream. In addition, they demonstrated that microspheres can move along the bifurcating areas of vessels in any direction.
Metin Sitti and his colleagues have been creating micro robots for drug delivery for several years. In 2018, scientists under his leadership created a micro robot based on bacteria associated with a flagellum and an erythrocyte with a drug and magnetic particles applied to it. The bacterium is responsible for movement, and the erythrocyte allows you to control the direction of this movement and the delivery of the active substance.
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