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

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

Journal

International Journal of Molecular Sciences
, E-ISSN: 1422-0067

Output data

Year: 2021, Volume: 22, Number: 14, Article number : 7326, Pages count : DOI: 10.3390/ijms22147326

Tags

Boron clusters; Boron neutron capture therapy; Cancer treatment; Cell‐specific aptamers; Drug delivery; Human glioblastoma cells

Authors

Vorobyeva M.A. ¹ , Dymova M.A. ¹ , Novopashina D.S. ¹ , Kuligina E.V. ¹ , Timoshenko V.V. ¹ , Kolesnikov I.A. ^1,2 , Taskaev S.Yu. ^2,3 , Richter V.A. ¹ , Venyaminova A.G. ¹

Affiliations

1	Institute of Chemical Biology and Fundamental Medicine, Siberian Division of Russian Academy of Sciences, Novosibirsk, 630090, Russian Federation
2	Budker Institute of Nuclear Physics, Siberian Division of the Russian Academy of Sciences, Novosibirsk, 630090, Russian Federation
3	Department of Physics, Novosibirsk State University, Novosibirsk, 630090, Russian Federation

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. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Vorobyeva M.A. , Dymova M.A. , Novopashina D.S. , Kuligina E.V. , Timoshenko V.V. , Kolesnikov I.A. , Taskaev S.Y. , Richter V.A. , Venyaminova A.G.
Tumor cell‐specific 2′‐fluoro rna aptamer conjugated with closo‐dodecaborate as a potential agent for boron neutron capture therapy
International Journal of Molecular Sciences. 2021. V.22. N14. 7326 . DOI: 10.3390/ijms22147326 WOS Scopus РИНЦ OpenAlex

Published print:

Jul 7, 2021

Web of science:	WOS:000676727200001
Scopus:	2-s2.0-85109073590
Elibrary:	46882007
OpenAlex:	W3179595187

DB	Citing
Scopus	18
Elibrary	19
Web of science	15
OpenAlex	18