Vital research
"We work on the production of nanocomposites - boron-containing quantum dots that will be designed for the diagnosis and boron neutron capture therapy of cancer (BNCT)," she began her speech. “Why is this area so relevant? Everyone knows that cancer ranks second after cardiology in mortality in the world. And the main method of treatment is still a combination of radiation and chemotherapy. Their action is not selective - together with cancer cells, healthy ones are also destroyed. Despite the obvious progress in the development of instrumental diagnostics of malignant neoplasms, there is a fairly high percentage of detection of this disease in the last stages. The development of new compact accelerator neutron sources has given impetus to the development of BNCT technology that is a method of selective destruction of malignant tumor cells and does not require surgical intervention."
E. D. Gribova said that this method of cancer treatment is based on the nuclear reaction of compounds containing the stable isotope boron-10 that proceeds under the influence of low-energy thermal neutrons. The reaction proceeds with the release of large energy, in total - almost 3 MeV but the linear transfer of energy is small, so only cancer cells are exposed. This high selectivity of the method allows you to treat such aggressive, inoperable cancer as glioblastoma, melanoma and others. There are clinically approved drugs - boron‑phenylalanine and sodium borocaptate - with their pros and cons, the most significant of the latter is their high cost. One injection of the first drug costs 250 thousand rubles, the second - about a million.
What are the advantages of BNCT? As the speaker emphasized, the body receives a minimum radiation dose, lower even than with the usual radiography procedure or with air travel; method enables cell‑level destruction of tumour and metastases. Since the current therapeutic preparations of boron are expensive, the further successful use of BNCT will depend on the production of effective boron-containing compounds. Such compounds can be boron‑containing nanoparticles, since the proportion of boron in them is much higher. Also, nanoparticles can be conjugated (that is, artificially to unite two molecules with different properties - O. T.) with biovectors that will deliver the drug to a cancerous tumor. Elena Dmitrievna dwelled on the advantages and disadvantages of boron carriers of different sizes. Small carriers easily penetrate cancer tissues and cells, but the removal of such drugs from the body is very fast. Large boron carriers are developed in many places in Russia and the world. Their advantage is a large specific content of boron and minimal withdrawal of the drug through the kidneys. The disadvantage is reduced permeability to cancer tissues and cells.
"What are we engaged in at Dubna University?" she continued. “In tandem with several Russian institutes and JINR, we work on the production of the drug and in the future, with its clinical investigations. This project consists of three blocks. Nuclear physics provides a therapeutic beam of epithermal neutrons that meet the requirements for use for BNCT. In the nano‑ and bioengineering unit, means for targeted delivery of boron based on quantum dots and protein vectors will be developed. The third unit includes biomedical investigations of bionic structures based on boron‑containing quantum dots and preclinical tests."
The first unit involves the development of compact accelerating neutron sources. S. Yu. Taskaev (G. I. Budker Institute of Nuclear Physics, Novosibirsk) is responsible for this part of the work and the facility is developed at the N. N. Blokhin National Medical Research Centre for Oncology in Moscow. The second unit is performed at the Department of Chemistry, New Technologies and Materials Science of the University. The speaker spoke about the requirements for BNCT agents. They should have a high absorption of thermal neutrons; to produce a high concentration of boron‑10 in cancer cells, in which it should be three times higher than in healthy ones; the concentration in the tumor throughout the duration of the BNCT should be constant, but after the end of therapy, the drug should be withdrawn quite quickly; have low systemic toxicity; the distribution of the drug in the body should not be registered invasively.
"We chose boron-containing nanoparticles for BNCT," E. D. Gribova emphasized. Why? They have a high boron content, they are not excreted through the kidneys during BNCT due to their size, and this is a fairly cheap agent. What boron-containing nanoparticles for BNCT are currently offered? These are boron‑based quantum dots, boron nanoparticles, boron carbide nanoparticles, boron‑doped carbon dots, boron‑doped magnetic nanoparticles, boron nanoparticles. Our collaborators chose boron‑containing quantum dots because they are biocompatible, have low cytotoxicity, high chemical stability and the ability to fine‑tune optical performance. Such quantum dots can be obtained from boron carbide, boron nitride and boron itself.
We are engaged in the synthesis of boron-containing quantum dots. To do this, boron is subjected to ultrasonic treatment, followed by solvothermal treatment at a temperature of 200 °C for 6 hours. The result is boron‑containing quantum dots ranging in size from 2.6 to 3.8 nm. Using capillary electrophoresis, the qualities of these points were evaluated, their optical properties were studied that should not interfere with the estimation of cancer cells, that is, for the diagnosis of cancer."
Elena Dmitrievna said that today, theoretical investigations are underway to improve the properties of quantum dots, work on targeted delivery of the drug to a cancer that allows therapy even at the last stage of the disease. To do this, boron quantum dots must be conjugated with biovectors that can be antibodies, protein molecules, amino acids. And since the technique of conjugating quantum dots with proteins has already been worked out, the specialists of the department decided to conjugate quantum dots with a low molecular weight vector such as folic acid. "We synthesized the conjugate, investigated its properties and today, its biological investigations (effects on cancer cells) are carried out at the State Research Centre "Vector" (Novosibirsk), "E. D. Gribova said.
She also presented the results of the work of the group of molecular dynamic investigations of protein‑protein interactions of FLNP that simulated the processes of uniting protein vectors. JINR employees are engaged in theoretical research. Specialists from Novosibirsk State University are also involved in the research.
The third unit - medical and biological is carried out with the participation of employees of the Blokhin Cancer Centre and the State Research Centre of the "Vector." Their task is to identify, construct and synthesize biovectors; estimation of toxicity of boron‑containing quantum dots and their conjugates; investigating the mechanisms of targeted delivery of engineered boron‑containing quantum dot conjugates to cancer cells. The expected scientific results will be used in the development of the technology and production of the third‑generation drug against cancer.
The report aroused great interest among those gathered in the conference hall of LRB. Elena Dmitrievna answered all the questions in detail, listened to comments and suggestions for the development of research.
Olga TARANTINA