Tumor cell‐specific 2′‐fluoro rna aptamer conjugated with closo‐dodecaborate as a potential agent for boron neutron capture therapy

Mariya A. Vorobyeva, Maya A. Dymova, Darya S. Novopashina, Elena V. Kuligina, Valentina V. Timoshenko, Iaroslav A. Kolesnikov, Sergey Yu Taskaev, Vladimir A. Richter, Alya G. Venyaminova

Результат исследования: Научные публикации в периодических изданияхстатьярецензирование

Аннотация

Boron neutron capture therapy (BNCT) is a binary radiotherapeutic approach to the treatment of malignant tumors, especially glioblastoma, the most frequent and incurable brain tumor. For successful BNCT, a boron‐containing therapeutic agent should provide selective and effective accumulation of10B isotope inside target cells, which are then destroyed after neutron irradiation. Nucleic acid aptamers look like very prospective candidates for carrying10B to the tumor cells. This study represents the first example of using 2′‐F‐RNA aptamer GL44 specific to the human glioblas-toma U‐87 MG cells as a boron delivery agent for BNCT. The closo‐dodecaborate residue was at-tached to the 5′‐end of the aptamer, which was also labeled by the fluorophore at the 3′‐end. The resulting bifunctional conjugate showed effective and specific internalization into U‐87 MG cells and low toxicity. After incubation with the conjugate, the cells were irradiated by epithermal neu-trons on the Budker Institute of Nuclear Physics neutron source. Evaluation of the cell proliferation by real‐time cell monitoring and the clonogenic test revealed that boron‐loaded aptamer decreased specifically the viability of U‐87 MG cells to the extent comparable to that of10B‐boronophenylala-nine taken as a control. Therefore, we have demonstrated a proof of principle of employing ap-tamers for targeted delivery of boron‐10 isotope in BNCT. Considering their specificity, ease of syn-thesis, and large toolkit of chemical approaches for high boron‐loading, aptamers provide a prom-ising basis for engineering novel BNCT agents.

Язык оригиналаанглийский
Номер статьи7326
ЖурналInternational Journal of Molecular Sciences
Том22
Номер выпуска14
DOI
СостояниеОпубликовано - 2 июл 2021

Предметные области OECD FOS+WOS

  • 1.06.CQ БИОХИМИЯ И МОЛЕКУЛЯРНАЯ БИОЛОГИЯ
  • 2.04 ХИМИЧЕСКИЕ ТЕХНОЛОГИИ
  • 1.04 ХИМИЧЕСКИЕ НАУКИ
  • 1.06 БИОЛОГИЧЕСКИЕ НАУКИ

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