Abstract
Introduction. Boron neutron capture therapy (bnct) is a promising method for treating tumors, in particular, infiltrative malignant tumors, due to the selective destruction of tumor cells without damaging the surrounding normal tissues. This type of therapy is based on nuclear reaction of neutron capture by stable 10b isotope. For the successful implementation of bnct, boron delivery drugs that must be selectively accumulated in malignant cells in a sufficient amount, and a neutron source with the energy required for the neutron capture reaction are needed. At the budker institute of nuclear physics, the accelerator-based neutron source was designed with flux parameters allowing studies on bnct to be conducted.Objective: to assess the effect of bnct on tumor and normal cell lines using borphenylalanine (bpa), borcaptate (bsh) and liposomal borcaptat as boron delivery drugs.Materials and methods. Human cell cultures: glioblastoma (u87), colorectal human adenocarcinoma (sw-620), human melanoma (sk-mel28) and primary embryonic cell lines were irradiated with a neutron flux at the presence of bpa, bsh and liposomal bsh with a concentration of 10b 40 μg/ml. The short-term cytotoxic effect of irradiation was evaluated using trypan blue. Cell survival 96 hours after irradiation was determined using mtt test, and survival fraction was evaluated using the clonogenic test.Results. Early cytotoxic effects of irradiation were not observed for all 4 cell lines. According to mtt and clonogenic tests, the most pronounced effect of bnct was noticed for sw-620 and u87 lines, regardless of boron delivery drug used. For sk-mel28 line, the best effect was achieved after irradiation with liposomal borocaptate. For the primary transplanted embryonic line, high toxicity was revealed when bnct was performed with borphenylalanine and borcaptate.Conclusion. The data obtained indicate that the accelerator-based bnct using boron delivery drugs, such as borphenylalanine, borcaptate and liposomal borcaptat, has a positive effect on tumor lines of glioblastoma, colorectal adenocarcinoma and melanoma.
Highlights
Boron neutron capture therapy (BNCT) is a promising method for treating tumors, in particular, infiltrative malignant tumors, due to the selective destruction of tumor cells without damaging the surrounding normal tissues
For the successful implementation of BNCT, boron delivery drugs that must be selectively accumulated in malignant cells in a sufficient amount, and a neutron source with the energy required for the neutron capture reaction are needed
Human cell cultures: glioblastoma (U87), colorectal human adenocarcinoma (SW-620), human melanoma (SK-Mel28) and primary embryonic cell lines were irradiated with a neutron flux at the presence of BPA, BSH and liposomal BSH with a concentration of 10B 40 μg/ml
Summary
Достигнутые параметры получаемого потока эпитепловых нейтронов позволили провести ряд исследований. Похожие результаты достигнуты для линии меланомы SK-Mel 28: доля выживших клеток снизилась значительно и составила в группах БНЗТ с BPA – 49 % и с BSH – 48 %. На 10-е сут, когда был закончен клоногенный тест для других клеточных линий, отмечалось уменьшение плотности монослоя и для нормальной линии во всех трех группах БНЗТ, особенно в группах с BPA и с BSH, также изменилась морфология клеток и снизилась степень их адгезии к пластику, что, вероятно, указывает на токсический эффект. В ходе анализа результатов клоногенного теста было выявлено, что доля выживших клеток в опытных группах с препаратами бора снизилась более чем на 50 % для всех трех опухолевых линий, что говорит о значительном влиянии БНЗТ на подавление способности клеток к пролиферации. Использование инкапсулированного в пегилированные липосомы BSH при проведении БНЗТ значительно снижало выживаемость всех 3 опухолевых линий, в то время как для первичной эмбриональной линии значимого цитотоксического эффекта не обнаружено.
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