Vitamin with poison
Scientists have found a way to increase the effectiveness of chemotherapy
NUST MISIS scientists have developed a way to significantly increase the susceptibility of cancer cells to antitumor drugs containing the active substance doxorubicin. To do this, the nanoparticles carrying the drug were enriched with folic acid, which cancer cells absorb about 1000 times more actively than ordinary ones.
The results of the study are published in the journal Nanomaterials (Permyakova et al., Plasma Surface Polymerized and Biomarker Conjugated Boron Nitride Nanoparticles for Cancer-Specific Therapy: Experimental and Theoretical Study).
Antitumor drugs containing the active substance doxorubicin are among the most widely used in the world. They are used for the treatment of leukemia, muscle cancer, sarcoma and a number of other malignant neoplasms. By itself, the active substance does not have a directed effect, that is, in its "pure form" when it enters the bloodstream, it actively binds to various compounds, and is also absorbed equally well by both affected and normal cells. This, first of all, means that large dosages are required to achieve the effect. In addition, the "illegibility" of doxorubicin is detrimental to healthy cells.
In 2017, a team of scientists from NUST MISIS, in collaboration with the N.N. Blokhin National Research Center of Oncology, conducted experiments on binding doxorubicin with biocompatible boron nitride nanoparticles, which perfectly combine with the drug due to a similar molecular structure. In vitro experiments were positive: it was shown that nanoparticles effectively deliver doxorubicin to cells and release the drug only after entering the cell, which will block the breakdown of doxorubicin in the bloodstream until the drug reaches the cells. Thus, the therapeutic dosage of the drug will decrease, but this will not solve all the problems: it was still necessary to "force" cancer cells to absorb the drug more actively than others; so actively that healthy cells do not have time to capture it.
Continuing the research, NUST MISIS scientists have found a way to "pack" doxorubicin so that its action becomes directed. The resulting method is based on the structural features of cancer cells: they divide extremely actively, and to obtain more nutrition, a huge number of folic acid receptors are located on their surface. It is better known to us as vitamin B9 – it is necessary for the growth and development of the circulatory and immune systems.
"Compared to healthy ones, there are about a thousand times more folic acid receptors on the surface of cancer cells," says Elizaveta Permyakova, one of the authors of the study, a researcher at the Inorganic Nanomaterials laboratory of NUST MISIS. – In our new study, we combined the properties of boron nitride and folic acid. First, we covalently attached folic acid to the nanoparticles, and then saturated this delivery system with doxorubicin."
The loading of nanoparticles with the preparation was evaluated using spectrophotometry: by itself, the active substance doxorubicin is a water-soluble compound of bright red color, thus, the aqueous solution of doxorubicin also has a rich red color. After adding boron nitride nanoparticles bound to folic acid to this solution, all doxorubicin binds to the particles, and the solution becomes transparent again. The use of this delivery system will reduce the nonspecific interactions of doxorubicin, as well as presumably increase the punctuality of drug delivery to cancer cells.
At the moment, to confirm the therapeutic activity, a series of in vitro experiments has been started in N.N. Blokhin National Research Center of Oncology using various cultures of human cancer cells.
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