TY - JOUR

T1 - Aptamers for Addressed Boron Delivery in BNCT: Effect of Boron Cluster Attachment Site on Functional Activity

AU - Novopashina, Darya S

AU - Dymova, Maya A

AU - Davydova, Anna S

AU - Meschaninova, Mariya I

AU - Malysheva, Daria O

AU - Kuligina, Elena V

AU - Richter, Vladimir A

AU - Kolesnikov, Iaroslav A

AU - Taskaev, Sergey Yu

AU - Vorobyeva, Mariya A

N1 - Funding: This research was funded by the Russian Science Foundation, grant number 19-74-20127.

PY - 2023/1

Y1 - 2023/1

N2 - Among the great variety of anti-cancer therapeutic strategies, boron neutron capture therapy (BNCT) represents a unique approach that doubles the targeting accuracy due to the precise positioning of a neutron beam and the addressed delivery of boron compounds. We have recently demonstrated the principal possibility of using a cell-specific 2'-F-RNA aptamer for the targeted delivery of boron clusters for BNCT. In the present study, we evaluated the amount of boron-loaded aptamer inside the cell via two independent methods: quantitative real-time polymerase chain reaction and inductive coupled plasma-atomic emission spectrometry. Both assays showed that the internalized boron level inside the cell exceeds 1 × 109 atoms/cell. We have synthesized closo-dodecaborate conjugates of 2'-F-RNA aptamers GL44 and Waz, with boron clusters attached either at the 3'- or at the 5'-end. The influence of cluster localization was evaluated in BNCT experiments on U-87 MG human glioblastoma cells and normal fibroblasts and subsequent analyses of cell viability via real-time cell monitoring and clonogenic assay. Both conjugates of GL44 aptamer provided a specific decrease in cell viability, while only the 3'-conjugate of the Waz aptamer showed the same effect. Thus, an individual adjustment of boron cluster localization is required for each aptamer. The efficacy of boron-loaded 2'-F-RNA conjugates was comparable to that of 10B-boronophenylalanine, so this type of boron delivery agent has good potential for BNCT due to such benefits as precise targeting, low toxicity and the possibility to use boron clusters made of natural, unenriched boron.

AB - Among the great variety of anti-cancer therapeutic strategies, boron neutron capture therapy (BNCT) represents a unique approach that doubles the targeting accuracy due to the precise positioning of a neutron beam and the addressed delivery of boron compounds. We have recently demonstrated the principal possibility of using a cell-specific 2'-F-RNA aptamer for the targeted delivery of boron clusters for BNCT. In the present study, we evaluated the amount of boron-loaded aptamer inside the cell via two independent methods: quantitative real-time polymerase chain reaction and inductive coupled plasma-atomic emission spectrometry. Both assays showed that the internalized boron level inside the cell exceeds 1 × 109 atoms/cell. We have synthesized closo-dodecaborate conjugates of 2'-F-RNA aptamers GL44 and Waz, with boron clusters attached either at the 3'- or at the 5'-end. The influence of cluster localization was evaluated in BNCT experiments on U-87 MG human glioblastoma cells and normal fibroblasts and subsequent analyses of cell viability via real-time cell monitoring and clonogenic assay. Both conjugates of GL44 aptamer provided a specific decrease in cell viability, while only the 3'-conjugate of the Waz aptamer showed the same effect. Thus, an individual adjustment of boron cluster localization is required for each aptamer. The efficacy of boron-loaded 2'-F-RNA conjugates was comparable to that of 10B-boronophenylalanine, so this type of boron delivery agent has good potential for BNCT due to such benefits as precise targeting, low toxicity and the possibility to use boron clusters made of natural, unenriched boron.

KW - Humans

KW - Boron/metabolism

KW - Boron Neutron Capture Therapy/methods

KW - Glioblastoma/metabolism

KW - Boron Compounds

KW - Oligonucleotides

KW - Phenylalanine/therapeutic use

KW - cancer treatment

KW - boron neutron capture therapy

KW - boron clusters

KW - glioblastoma

KW - cell-specific aptamers

KW - boron delivery agents

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-85145923820&origin=inward&txGid=ef2e5921afd58977f8287134cb6551aa

UR - https://elibrary.ru/item.asp?id=50369635

UR - https://www.mendeley.com/catalogue/c1c94667-5b03-39e1-8790-d0d0ee28110b/

U2 - 10.3390/ijms24010306

DO - 10.3390/ijms24010306

M3 - Article

C2 - 36613750

VL - 24

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 1

M1 - 306

ER -