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Molecules 2017, 22(9), 1393;

High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents

Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Bioorganic Chemistry, Sienkiewicza 112, 90-363 Lodz, Poland
Institute of Medical Biology of the Polish Academy of Sciences, Laboratory of Molecular Virology and Biological Chemistry, 106 Lodowa St., 92-232 Lodz, Poland
This paper is dedicated to Prof. Dr. Li He Zhang on the occasion of his 80th birthday and in recognition of his outstanding contributions to nucleoside and nucleic acid chemistry.
Current address: Centre of New Technologies, University of Warsaw, S. Banacha 2c, 02-097 Warsaw, Poland.
Authors to whom correspondence should be addressed.
Received: 18 July 2017 / Accepted: 14 August 2017 / Published: 23 August 2017
(This article belongs to the Special Issue Synthesis and Applications of Oligonucleotide Conjugates)
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Boron cluster-modified therapeutic nucleic acids with improved properties are of interest in gene therapy and in cancer boron neutron capture therapy (BNCT). High metallacarborane-loaded antisense oligonucleotides (ASOs) targeting epidermal growth factor receptor (EGFR) were synthesized through post-synthetic Cu (I)-assisted “click” conjugation of alkyne-modified DNA-oligonucleotides with a boron cluster alkyl azide component. The obtained oligomers exhibited increased lipophilicity compared to their non-modified precursors, while their binding affinity to complementary DNA and RNA strands was slightly decreased. Multiple metallacarborane residues present in the oligonucleotide chain, each containing 18 B-H groups, enabled the use of IR spectroscopy as a convenient analytical method for these oligomers based on the diagnostic B-H signal at 2400–2650 cm−1. The silencing activity of boron cluster-modified ASOs used at higher concentrations was similar to that of unmodified oligonucleotides. The screened ASOs, when used in low concentrations (up to 50 μM), exhibited pro-oxidative properties by inducing ROS production and an increase in mitochondrial activities in HeLa cells. In contrast, when used at higher concentrations, the ASOs exhibited anti-oxidative properties by lowering ROS species levels. In the HeLa cells (tested in the MTT assay) treated (without lipofectamine) or transfected with the screened compounds, the mitochondrial activity remained equal to the control level or only slightly changed (±30%). These findings may be useful in the design of dual-action boron cluster-modified therapeutic nucleic acids with combined antisense and anti-oxidant properties. View Full-Text
Keywords: metallacarborane; antisense oligonucleotide; BNCT; ROS; EGFR metallacarborane; antisense oligonucleotide; BNCT; ROS; EGFR

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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Kaniowski, D.; Ebenryter-Olbińska, K.; Sobczak, M.; Wojtczak, B.; Janczak, S.; Leśnikowski, Z.J.; Nawrot, B. High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents. Molecules 2017, 22, 1393.

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