TY - JOUR

T1 - Tumor cell‐specific 2′‐fluoro rna aptamer conjugated with closo‐dodecaborate as a potential agent for boron neutron capture therapy

AU - Vorobyeva, Mariya A.

AU - Dymova, Maya A.

AU - Novopashina, Darya S.

AU - Kuligina, Elena V.

AU - Timoshenko, Valentina V.

AU - Kolesnikov, Iaroslav A.

AU - Taskaev, Sergey Yu

AU - Richter, Vladimir A.

AU - Venyaminova, Alya G.

N1 - Funding Information: Funding: This research was funded by the Russian Science Foundation, grant number 19‐74‐20127. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/7/2

Y1 - 2021/7/2

N2 - 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.

AB - 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.

KW - Boron clusters

KW - Boron neutron capture therapy

KW - Cancer treatment

KW - Cell‐specific aptamers

KW - Drug delivery

KW - Human glioblastoma cells

KW - Cell Line

KW - Isotopes/pharmacology

KW - Boron Neutron Capture Therapy/methods

KW - Humans

KW - Neutrons/therapeutic use

KW - Boron Compounds/pharmacology

KW - Glioblastoma/radiotherapy

KW - Aptamers, Nucleotide/pharmacology

KW - Brain Neoplasms/rehabilitation

KW - Boron/pharmacology

KW - Cell Line, Tumor

KW - Cell Proliferation/radiation effects

UR - http://www.scopus.com/inward/record.url?scp=85109073590&partnerID=8YFLogxK

U2 - 10.3390/ijms22147326

DO - 10.3390/ijms22147326

M3 - Article

C2 - 34298946

AN - SCOPUS:85109073590

VL - 22

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 14

M1 - 7326

ER -