Yttrium against cancer
Russian Yttrium Nanoparticles Find and Kill Cancer by Beta Decay
Pseudomonas Aeruginosa toxin helps them to find a target
Employees of the Lobachevsky Nizhny Novgorod State University, the Federal Research Center "Crystallography and Photonics" of the Russian Academy of Sciences, the Institute of Bioorganic Chemistry of the Russian Academy of Sciences, the St. Petersburg Academic University - the Scientific and Educational Center of Nanotechnology of the Russian Academy of Sciences and a number of other research organizations in Russia and Australia have created nanoparticles based on yttrium, allowing to simultaneously identify the size and position tumors and deliver to them funds for chemotherapy. These particles have shown their effectiveness both "in vitro" and in living organisms. The scientific article was published in the journal Proceedings of the National Academy of Sciences (PNAS).
The closer in structure the causative agent of the disease is to the affected organism, the more difficult it is to get rid of it and at the same time not to harm the "native" cells. Therefore, existing cancer treatments have so many side effects: in addition to tumor cells, they affect healthy cells. To reduce the number and degree of manifestation of such effects, methods of targeted drug delivery are being developed.
One of the promising directions in this regard is nanoparticles capable of recognizing cells of a certain type, binding to them and releasing radioactive substances or chemotherapy agents in their immediate vicinity. Since these nanoparticles must independently detect their targets, we can say that they have a diagnostic function in addition to the therapeutic function. The direction in medicine, involving simultaneous therapy and diagnosis, is called theranostics.
The authors of the new work created and tested the effectiveness of nanoparticles for theranostics. The particles with an average diameter of 50 nm (they were also collected in groups with a diameter of about 250 nm) were based on yttrium (Y) compounds with the addition of ytterbium (Yb) and thulium (Tm) ions. Under the action of radiation with a wavelength of 980 nm, Yb and Tm ions glowed. This made it possible to determine the location of nanoparticles in the body of the experimental animal.
The nanoparticles contained several isotopes of yttrium, one of which, Y-90, has radioactivity: an electron and an antineutrino are split off from it and it becomes zirconium-90. This beta decay reaction damages nearby cells.
Another group of the obtained nanoparticles carried a chemotherapy agent – a modified Pseudomonas aeruginosa Pseudomonas aeruginosa toxin, DARPin-PE40, whose anti-cancer effect has already been confirmed in previous studies. This toxin consists of two proteins connected by a jumper of 8-10 nm. The function of DARPin is to detect HER2 receptors, which are especially numerous on breast cancer cells. And PE40 stops protein synthesis, preventing ribosomes from lengthening chains of amino acids.
The particles of the third group combined both radioactive yttrium and bacterial poisons. Thus, in theory, they had to independently detect breast cancer cells by receptors on their surface, and then act on them with both "chemistry" and radiation.
The fact that these processes are actually being realized was confirmed on SK-BR-3 cell cultures (cells taken from the metastases of a 43-year-old breast cancer patient) and in the organisms of mice that had a tumor transplanted from the same cells (the thymus gland was previously removed from rodents, so foreign tumors were not rejected from them). As a control in the first case, the cells of the ovarian epithelium of the Chinese hamster Cho, which do not have HER2 receptors, were used. In the second case, nanoparticles were injected directly into the tumor to reduce the possible toxic effect on the rodent's body. Therefore, there was no control group of animals – they simply lacked tumors, that is, places for injecting drugs.
Scientists have not only shown that nanoparticles with radioactive yttrium and modified Pseudomonas aeruginosa toxin kill breast tumor cells, but also determined their optimal doses. It turned out that the most effective nanoparticles are those that combine chemotherapy (DARPin-PE40) and radiation therapy (Y-90). It was enough to inject only 0.0024 micrograms of combined nanoparticles per milliliter of solution to destroy half of the tumor cells in vitro.
Drawing from an article in PNAS – VM
Nanoparticles containing only yttrium or only bacterial toxin had to be injected at concentrations thousands of times higher – 140 micrograms/ml and 5.2 micrograms/ml, respectively. And to reduce tumors in vivo, 10-15 micrograms of nanoparticles per gram of animal weight were required.
Thus, Russian researchers have made a significant step towards the development of nanoparticles for theranostics in oncology. Now their invention must undergo preclinical studies, and if they are successfully completed, they can be followed by clinical ones.
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