Composites of Nucleic Acids and Boron Clusters (C<sub>2</sub>B<sub>10</sub>H<sub>12</sub>) as Functional Nanoparticles for Downregulation of EGFR Oncogene in Cancer Cells
Epidermal growth factor receptor (EGFR) is one of the most promising molecular targets for anticancer therapy. We used boron clusters as a platform for generation of new materials. For this, functional DNA constructs conjugated with boron clusters (B-ASOs) were developed. These B-ASOs, built from 1,...
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MDPI AG
2021-05-01
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| author | Damian Kaniowski Katarzyna Ebenryter-Olbińska Katarzyna Kulik Justyna Suwara Wojciech Cypryk Agata Jakóbik-Kolon Zbigniew Leśnikowski Barbara Nawrot |
| author_facet | Damian Kaniowski Katarzyna Ebenryter-Olbińska Katarzyna Kulik Justyna Suwara Wojciech Cypryk Agata Jakóbik-Kolon Zbigniew Leśnikowski Barbara Nawrot |
| author_sort | Damian Kaniowski |
| collection | DOAJ |
| description | Epidermal growth factor receptor (EGFR) is one of the most promising molecular targets for anticancer therapy. We used boron clusters as a platform for generation of new materials. For this, functional DNA constructs conjugated with boron clusters (B-ASOs) were developed. These B-ASOs, built from 1,2-dicarba-<i>closo</i>-dodecaborane linked with two anti-EGFR antisense oligonucleotides (ASOs), form with their complementary congeners torus-like nanostructures, as previously shown by atomic force microscope (AFM) and transmission electron cryo-microscopy (cryo-TEM) imaging. In the present work, deepened studies were carried out on B-ASO’s properties. In solution, B-ASOs formed four dominant complexes as confirmed by non-denaturing polyacrylamide gel electrophoresis (PAGE). These complexes exhibited increased stability in cell lysate comparing to the non-modified ASO. Fluorescently labeled B-ASOs localized mostly in the cytoplasm and decreased EGFR expression by activating RNase H. Moreover, the B-ASO complexes altered the cancer cell phenotype, decreased cell migration rate, and arrested the cells in the S phase of cell cycle. The 1,2-dicarba-<i>closo</i>-dodecaborane-containing nanostructures did not activate NLRP3 inflammasome in human macrophages. In addition, as shown by inductively coupled plasma mass spectrometry (ICP MS), these nanostructures effectively penetrated the human squamous carcinoma cells (A431), showing their potential applicability as anticancer agents. |
| first_indexed | 2024-03-10T11:42:00Z |
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| language | English |
| last_indexed | 2024-03-10T11:42:00Z |
| publishDate | 2021-05-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-032067c5b0d447ae8461bf7c9bd32ab72023-11-21T18:20:57ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-01229486310.3390/ijms22094863Composites of Nucleic Acids and Boron Clusters (C<sub>2</sub>B<sub>10</sub>H<sub>12</sub>) as Functional Nanoparticles for Downregulation of EGFR Oncogene in Cancer CellsDamian Kaniowski0Katarzyna Ebenryter-Olbińska1Katarzyna Kulik2Justyna Suwara3Wojciech Cypryk4Agata Jakóbik-Kolon5Zbigniew Leśnikowski6Barbara Nawrot7Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, PolandCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, PolandCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, PolandCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, PolandCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, PolandDepartment of Inorganic, Analytical Chemistry and Electrochemistry, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 6, 44-100 Gliwice, PolandLaboratory of Medicinal Chemistry, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 92-232 Lodz, PolandCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, PolandEpidermal growth factor receptor (EGFR) is one of the most promising molecular targets for anticancer therapy. We used boron clusters as a platform for generation of new materials. For this, functional DNA constructs conjugated with boron clusters (B-ASOs) were developed. These B-ASOs, built from 1,2-dicarba-<i>closo</i>-dodecaborane linked with two anti-EGFR antisense oligonucleotides (ASOs), form with their complementary congeners torus-like nanostructures, as previously shown by atomic force microscope (AFM) and transmission electron cryo-microscopy (cryo-TEM) imaging. In the present work, deepened studies were carried out on B-ASO’s properties. In solution, B-ASOs formed four dominant complexes as confirmed by non-denaturing polyacrylamide gel electrophoresis (PAGE). These complexes exhibited increased stability in cell lysate comparing to the non-modified ASO. Fluorescently labeled B-ASOs localized mostly in the cytoplasm and decreased EGFR expression by activating RNase H. Moreover, the B-ASO complexes altered the cancer cell phenotype, decreased cell migration rate, and arrested the cells in the S phase of cell cycle. The 1,2-dicarba-<i>closo</i>-dodecaborane-containing nanostructures did not activate NLRP3 inflammasome in human macrophages. In addition, as shown by inductively coupled plasma mass spectrometry (ICP MS), these nanostructures effectively penetrated the human squamous carcinoma cells (A431), showing their potential applicability as anticancer agents.https://www.mdpi.com/1422-0067/22/9/4863antisense oligonucleotideboron clusternanostructureEGFRmacrophagescellular uptake |
| spellingShingle | Damian Kaniowski Katarzyna Ebenryter-Olbińska Katarzyna Kulik Justyna Suwara Wojciech Cypryk Agata Jakóbik-Kolon Zbigniew Leśnikowski Barbara Nawrot Composites of Nucleic Acids and Boron Clusters (C<sub>2</sub>B<sub>10</sub>H<sub>12</sub>) as Functional Nanoparticles for Downregulation of EGFR Oncogene in Cancer Cells International Journal of Molecular Sciences antisense oligonucleotide boron cluster nanostructure EGFR macrophages cellular uptake |
| title | Composites of Nucleic Acids and Boron Clusters (C<sub>2</sub>B<sub>10</sub>H<sub>12</sub>) as Functional Nanoparticles for Downregulation of EGFR Oncogene in Cancer Cells |
| title_full | Composites of Nucleic Acids and Boron Clusters (C<sub>2</sub>B<sub>10</sub>H<sub>12</sub>) as Functional Nanoparticles for Downregulation of EGFR Oncogene in Cancer Cells |
| title_fullStr | Composites of Nucleic Acids and Boron Clusters (C<sub>2</sub>B<sub>10</sub>H<sub>12</sub>) as Functional Nanoparticles for Downregulation of EGFR Oncogene in Cancer Cells |
| title_full_unstemmed | Composites of Nucleic Acids and Boron Clusters (C<sub>2</sub>B<sub>10</sub>H<sub>12</sub>) as Functional Nanoparticles for Downregulation of EGFR Oncogene in Cancer Cells |
| title_short | Composites of Nucleic Acids and Boron Clusters (C<sub>2</sub>B<sub>10</sub>H<sub>12</sub>) as Functional Nanoparticles for Downregulation of EGFR Oncogene in Cancer Cells |
| title_sort | composites of nucleic acids and boron clusters c sub 2 sub b sub 10 sub h sub 12 sub as functional nanoparticles for downregulation of egfr oncogene in cancer cells |
| topic | antisense oligonucleotide boron cluster nanostructure EGFR macrophages cellular uptake |
| url | https://www.mdpi.com/1422-0067/22/9/4863 |
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