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Vorobyeva M.A., Dymova M.A., Novopashina D.S. et al.
Oligonucleotide aptamers as novel cell-specific delivery agents for boron neutron capture therapy
© VOROBYEVA M.A., DYMOVA M.A., NOVOPASHINA D.S., KULIGINA E.V., KOLESNIKOV I.A., TASKAEV S.YU., RICHTER V.A., MESCHANINOVA M.I. UDC 577.29
DOI: 10.20333/25000136-2022-5-108
Oligonucleotide aptamers as novel cell-specific delivery agents for boron neutron capture therapy
M.A. Vorobyeva1*, M.A. Dymova1, D.S. Novopashina1, E.V. Kuligina1, I.A. Kolesnikov1,2, S.Yu. Taskaev2, V.A. Richter1, M.I. Meschaninova1
1 Institute of Chemical Biology and Fundamental Medicine SD RAS, Novosibirsk 630090, Russian Federation
2 Budker Institute of Nuclear Physics SD RAS, Novosibirsk 630090, Russian Federation
Abstract. Oligonucleotide aptamers seem to be promising delivery vehicles addressing boron compounds to tumour cells for boron neutron capture therapy (BNCT). Here, we report the first example of using 2'-F-RNA aptamer specific to human glioblastoma cells as a delivery agent for boron clusters, which provides cell internalisation sufficient for the BNCT model.
Key words: cell-specific aptamers, human glioblastoma cells, boron clusters, boron neutron capture therapy, cancer treatment, drug delivery. Conflict of interest. The authors declare the absence of obvious and potential conflicts of interest associated with publication of this article. Citation: Vorobyeva MA, Dymova MA, Novopashina DS, Kuligina EV, Kolesnikov IA, Taskaev SYu, Richter VA, Meschaninova MI. Oligonucleotide aptamers as novel cell-specific delivery agents for boron neutron capture therapy. Siberian Medical Review. 2022;(5):108. DOI: 10.20333/25000136-2022-5-108
Boron neutron capture therapy (BNCT) represents a promising approach to treating malignant tumours, particularly glioblastoma: the most frequent and incurable brain tumour [1]. For effective BNCT, a boron-containing therapeutic agent should provide selective and effective accumulation of 10B isotope inside target tumour cells, which are then destroyed after irradiation by an epither-mal neutron beam. Nucleic acid aptamers are very promising candidates for selective delivery of 10B compounds to tumour cells.
We employed a 2'-F-RNA aptamer specific to human glioblastoma U-87 MG cells as a delivery vehicle for a boron cluster covalently attached to the 5'-end of the aptamer through the click reaction between the 5'-alkyne-modified aptamer and azide-containing derivative of closo-dodeca-borate [2]. Cluster-conjugated aptamer demonstrated effective and specific internalisation into U-87 MG cells and low toxicity. To establish the proof-of-principle of using boron-loaded aptamers for BNCT, the cells were incubated with the conjugate and irradiated on the Budker Institute of Nuclear Physics (BINP) neutron source. Then, cell proliferation was assessed through real-time cell monitoring and the clonogenic test. The results showed that boron-loaded aptamer specifically decreased the viability of U-87 MG cells to an extent comparable to that of 10B-bor-onophenylalanine taken as a control.
Our study provides the first example of employing nucleic acid aptamer as a cell-specific boron carrier for BNCT. Taking into account their specificity, versatility, ease of chemical synthesis and large possibilities for high boron-loading, aptamers provide an up-and-coming basis for engineering novel BNCT agents.
This research was funded by the Russian Science Foundation, grant number 19-74-20127.
References
1. Dymova MA, Taskaev SY, Richter VA, Kuligina EV. Boron neutron capture therapy: Current status and future perspectives. Cancer Communications. 2020;(40):406-21.
2. Novopashina DS, Vorobyeva MA, Lomzov AA, Silnikov VN, Venyaminova AG. Terminal mono- and bis-conjugates of oligonucleotides with closo-dodecabo-rate: synthesis and physico-chemical properties. International Journal of Molecular Sciences. 2020;(22):182.
Author information
Maria A. Vorobyeva, senior researcher, Institute of Chemical Biology and Fundamental Medicine SD RAS; Address: 8, Lavrentiev Avenue, Novosibirsk, Russian Federation 630090; Phone: +7(383)3635129; e-mail: maria@vorobyeva.ru, http://orcid.org/ 0000-0001-5317-3288 Maya A. Dymova, senior researcher, Institute of Chemical Biology and Fundamental Medicine SD RAS; Address: 8, Lavrentiev Avenue, Novosibirsk, Russian Federation 630090; Phone: +7(383)3635189; e-mail: maya.a.rot@gmail.com
Darya S. Novopashina, senior researcher, Institute of Chemical Biology and Fundamental Medicine SD RAS; Address: 8, Lavrentiev Avenue, Novosibirsk, Russian Federation 630090; Phone: +7(383)3635129; e-mail: danov@niboch.nsc.ru
Elena V. Kuligina, senior researcher, Institute of Chemical Biology and Fundamental Medicine SD RAS; Address: 8, Lavrentiev Avenue, Novosibirsk, Russian Federation 630090; Phone: +7(383)3635190; e-mail: kuligina@niboch.nsc.ru
Iaroslav A. Kolesnikov, graduate student, Institute of Chemical Biology and Fundamental Medicine SD RAS; Address: 8, Lavrentiev Avenue, Novosibirsk, Russian Federation 630090; Budker Institute of Nuclear Physics SD RAS; Address: 11, Lavrentiev Avenue, Novosibirsk, Russian Federation 630090; Phone: +7(383)3635129; e-mail: katyono@mail.ru
Sergey Yu. Taskaev, head of the laboratory, Budker Institute of Nuclear Physics SD RAS; Address: 11, Lavrentiev Avenue, Novosibirsk, Russian Federation 630090; Phone: +7(383) 3294121; e-mail: S.Yu.Taskaev@inp.nsk.su
Vladimir A. Richter, head of the laboratory, Institute of Chemical Biology and Fundamental Medicine SD RAS; Address: 8, Lavrentiev Avenue, Novosibirsk, Russian Federation 630090; Phone: +7(383)3635152; e-mail: richter@niboch.nsc.ru
Maria I. Meschaninova, senior researcher, Institute of Chemical Biology and Fundamental Medicine SD RAS; Address: 8, Lavrentiev Avenue, Novosibirsk, Russian Federation 630090; Phone: +7(383)3635129; e-mail: mesch@niboch.nsc.ru
Received 18 June 2022 Revision Received 21 August 2022 Accepted 30 August 2022
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Siberian Medical Review. 2022;(5):108
