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Composites of Nucleic Acids and Boron Clusters (C2B10H12) as Functional Nanoparticles for Downregulation of EGFR Oncogene in Cancer Cells
Authors:Damian Kaniowski,Katarzyna Ebenryter-Olbi&#x  ska,Katarzyna Kulik,Justyna Suwara,Wojciech Cypryk,Agata Jak  bik-Kolon,Zbigniew Le   nikowski,Barbara Nawrot
Affiliation:1.Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Lodz, Poland; (D.K.); (K.E.-O.); (K.K.); (J.S.); (W.C.);2.Department of Inorganic, Analytical Chemistry and Electrochemistry, Faculty of Chemistry, Silesian University of Technology, Krzywoustego 6, 44-100 Gliwice, Poland;3.Laboratory of Medicinal Chemistry, Institute of Medical Biology, Polish Academy of Sciences, Lodowa 106, 92-232 Lodz, Poland;
Abstract: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-closo-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-closo-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.
Keywords:antisense oligonucleotide   boron cluster   nanostructure   EGFR   macrophages   cellular uptake
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