Cage Hunting: "beaters" and "numbers"
Nanorobots play tag with cells
Kirill Stasevich, CompulentaAll cells, including cancer cells, carry specific molecules on their surface, by which one type of cell can be distinguished from another.
But the problem is that taken separately, such signs do not work. That is, it is impossible to distinguish a cancer cell from a healthy one by any particular membrane protein with absolute accuracy, because there will definitely be a healthy cell with the same "cancer" protein. And if we use an anti-cancer drug that recognizes diseased cells only by one sign, then we risk "mowing down" a lot of normal cells as well.
In other words, when hunting for tumor cells, and indeed for any type of cell, you need to focus immediately on a complex of molecular signs in order to make fewer mistakes. For example, it is better to look for not one protein on the membrane, but five or six at once. Usually, to recognize a cell, a special molecule (for example, an antibody) is constructed, which connects to the cell through its specific protein and attaches a drug cargo to it. It is easy to create such a molecule if we are talking about a single protein, but it is much more difficult to do something that would interact with 5-6 proteins at once.
Researchers from Columbia University (USA) tried to go around and instead of one complex molecule, they constructed several simple ones so that they worked together, like a robot (or automaton, as the authors themselves say). Milan Stojanovic and his collaborators obtained three chimeric molecules that consisted of antibodies and DNA fragments attached to them. Each antibody recognized a specific membrane protein.
When all three molecules were on the same cell, an exchange reaction took place between them. Another DNA molecule started this reaction, which floated freely around and did not interact with the cell: she was pulling on a certain chain of DNA attached to one of the antibodies. The DNA chain remaining with the antibody pulled one of the chains from the neighboring DNA-antibody chimera, which sat on another membrane protein. This second one took the chain from the third chimera. But the third one filled the vacant space with a DNA chain from a free-floating molecule (already another one), but this time the selected chain carried a fluorescent label. While the label was floating freely in the solution, it did not glow, but as soon as it combined with DNA on a chimeric molecule, it immediately began to fluoresce.
The sequence of the exchange reaction between three chimeric DNA-antibody molecules on the cell surface,
leading to the appearance of a glowing mark (F) on the cell (figure of the authors of the work).
As a result of the described reassembly-rearrangement of several molecules, a luminous label was attached to the cell, by which this cell could be recognized (to find out, among other things, whether there is such a cell in the sample at all). The whole reaction took about 15 minutes. If at least one of the surface proteins was missing on the cell, the reaction did not go on – because then one of the exchange participants did not sit on the cell.
The researchers conducted their experiments on ordinary blood cells, but the same can be done with any cells, including cancer cells. Moreover, the recognition accuracy can be improved by using antibodies against four, five or even six membrane proteins. And instead of a fluorescent label, you can, for example, hang some kind of toxin that kills a tumor cell. In general, the prospects for the method are huge, the main thing is that it works not only in a test tube, but also in a living organism.
The results of the study are published in the journal Nature Nanotechnology: Maria Rudchenko et al., Autonomous molecular cascades for evaluation of cell surfaces.
Prepared based on materials from Columbia University: DNA Robots Find and Tag Blood Cells.
Portal "Eternal youth" http://vechnayamolodost.ru12.08.2013