High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents
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...
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MDPI AG
2017-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/22/9/1393 |
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| author | Damian Kaniowski Katarzyna Ebenryter-Olbińska Milena Sobczak Błażej Wojtczak Sławomir Janczak Zbigniew J. Leśnikowski Barbara Nawrot |
| author_facet | Damian Kaniowski Katarzyna Ebenryter-Olbińska Milena Sobczak Błażej Wojtczak Sławomir Janczak Zbigniew J. Leśnikowski Barbara Nawrot |
| author_sort | Damian Kaniowski |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T11:46:58Z |
| format | Article |
| id | doaj.art-22ef745e285a44598e790c9ec3d4e5c8 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-04-13T11:46:58Z |
| publishDate | 2017-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-22ef745e285a44598e790c9ec3d4e5c82022-12-22T02:48:10ZengMDPI AGMolecules1420-30492017-08-01229139310.3390/molecules22091393molecules22091393High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer AgentsDamian Kaniowski0Katarzyna Ebenryter-Olbińska1Milena Sobczak2Błażej Wojtczak3Sławomir Janczak4Zbigniew J. Leśnikowski5Barbara Nawrot6Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Bioorganic Chemistry, Sienkiewicza 112, 90-363 Lodz, PolandCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Bioorganic Chemistry, Sienkiewicza 112, 90-363 Lodz, PolandCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Bioorganic Chemistry, Sienkiewicza 112, 90-363 Lodz, PolandInstitute of Medical Biology of the Polish Academy of Sciences, Laboratory of Molecular Virology and Biological Chemistry, 106 Lodowa St., 92-232 Lodz, PolandInstitute of Medical Biology of the Polish Academy of Sciences, Laboratory of Molecular Virology and Biological Chemistry, 106 Lodowa St., 92-232 Lodz, PolandInstitute of Medical Biology of the Polish Academy of Sciences, Laboratory of Molecular Virology and Biological Chemistry, 106 Lodowa St., 92-232 Lodz, PolandCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Department of Bioorganic Chemistry, Sienkiewicza 112, 90-363 Lodz, PolandBoron 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.https://www.mdpi.com/1420-3049/22/9/1393metallacarboraneantisense oligonucleotideBNCTROSEGFR |
| spellingShingle | Damian Kaniowski Katarzyna Ebenryter-Olbińska Milena Sobczak Błażej Wojtczak Sławomir Janczak Zbigniew J. Leśnikowski Barbara Nawrot High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents Molecules metallacarborane antisense oligonucleotide BNCT ROS EGFR |
| title | High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents |
| title_full | High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents |
| title_fullStr | High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents |
| title_full_unstemmed | High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents |
| title_short | High Boron-loaded DNA-Oligomers as Potential Boron Neutron Capture Therapy and Antisense Oligonucleotide Dual-Action Anticancer Agents |
| title_sort | high boron loaded dna oligomers as potential boron neutron capture therapy and antisense oligonucleotide dual action anticancer agents |
| topic | metallacarborane antisense oligonucleotide BNCT ROS EGFR |
| url | https://www.mdpi.com/1420-3049/22/9/1393 |
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