Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells

The application of siRNA in gene therapy is mainly limited because of the problems with its transport into cells. Utilization of cationic dendrimers as siRNA carriers seems to be a promising solution in overcoming these issues, due to their positive charge and ability to penetrate cell membranes. Th...

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Main Authors: Kamila Białkowska, Katarzyna Miłowska, Sylwia Michlewska, Paulina Sokołowska, Piotr Komorowski, Tania Lozano-Cruz, Rafael Gomez-Ramirez, Francisco Javier de la Mata, Maria Bryszewska
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/13/7097
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author Kamila Białkowska
Katarzyna Miłowska
Sylwia Michlewska
Paulina Sokołowska
Piotr Komorowski
Tania Lozano-Cruz
Rafael Gomez-Ramirez
Francisco Javier de la Mata
Maria Bryszewska
author_facet Kamila Białkowska
Katarzyna Miłowska
Sylwia Michlewska
Paulina Sokołowska
Piotr Komorowski
Tania Lozano-Cruz
Rafael Gomez-Ramirez
Francisco Javier de la Mata
Maria Bryszewska
author_sort Kamila Białkowska
collection DOAJ
description The application of siRNA in gene therapy is mainly limited because of the problems with its transport into cells. Utilization of cationic dendrimers as siRNA carriers seems to be a promising solution in overcoming these issues, due to their positive charge and ability to penetrate cell membranes. The following two types of carbosilane dendrimers were examined: CBD-1 and CBD-2. Dendrimers were complexed with pro-apoptotic siRNA (Mcl-1 and Bcl-2) and the complexes were characterized by measuring their zeta potential, circular dichroism and fluorescence of ethidium bromide associated with dendrimers. CBD-2/siRNA complexes were also examined by agarose gel electrophoresis. Both dendrimers form complexes with siRNA. Moreover, the cellular uptake and influence on the cell viability of the dendrimers and dendriplexes were evaluated using microscopic methods and XTT assay on MCF-7 cells. Microscopy showed that both dendrimers can transport siRNA into cells; however, a cytotoxicity assay showed differences in the toxicity of these dendrimers.
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spelling doaj.art-4994b99565a441c9a5bbddc8630791352023-11-22T02:40:06ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-07-012213709710.3390/ijms22137097Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 CellsKamila Białkowska0Katarzyna Miłowska1Sylwia Michlewska2Paulina Sokołowska3Piotr Komorowski4Tania Lozano-Cruz5Rafael Gomez-Ramirez6Francisco Javier de la Mata7Maria Bryszewska8Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, PolandDepartment of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, PolandLaboratory of Microscopic Imaging and Specialized Biological Techniques, Faculty of Biology and Environmental Protection, University of Lodz, Banacha12/16, 90-237 Lodz, PolandMolecular and Nanostructural Biophysics Laboratory, “Bionanopark” Ldt., 114/116 Dubois St., 93-465 Lodz, PolandMolecular and Nanostructural Biophysics Laboratory, “Bionanopark” Ldt., 114/116 Dubois St., 93-465 Lodz, PolandDepartment of Organic and Inorganic Chemistry, IQAR, University of Alcalá, 28805 Madrid, SpainDepartment of Organic and Inorganic Chemistry, IQAR, University of Alcalá, 28805 Madrid, SpainDepartment of Organic and Inorganic Chemistry, IQAR, University of Alcalá, 28805 Madrid, SpainDepartment of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska St., 90-236 Lodz, PolandThe application of siRNA in gene therapy is mainly limited because of the problems with its transport into cells. Utilization of cationic dendrimers as siRNA carriers seems to be a promising solution in overcoming these issues, due to their positive charge and ability to penetrate cell membranes. The following two types of carbosilane dendrimers were examined: CBD-1 and CBD-2. Dendrimers were complexed with pro-apoptotic siRNA (Mcl-1 and Bcl-2) and the complexes were characterized by measuring their zeta potential, circular dichroism and fluorescence of ethidium bromide associated with dendrimers. CBD-2/siRNA complexes were also examined by agarose gel electrophoresis. Both dendrimers form complexes with siRNA. Moreover, the cellular uptake and influence on the cell viability of the dendrimers and dendriplexes were evaluated using microscopic methods and XTT assay on MCF-7 cells. Microscopy showed that both dendrimers can transport siRNA into cells; however, a cytotoxicity assay showed differences in the toxicity of these dendrimers.https://www.mdpi.com/1422-0067/22/13/7097siRNAcarbosilane dendrimersdendriplexesnanocarriers
spellingShingle Kamila Białkowska
Katarzyna Miłowska
Sylwia Michlewska
Paulina Sokołowska
Piotr Komorowski
Tania Lozano-Cruz
Rafael Gomez-Ramirez
Francisco Javier de la Mata
Maria Bryszewska
Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells
International Journal of Molecular Sciences
siRNA
carbosilane dendrimers
dendriplexes
nanocarriers
title Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells
title_full Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells
title_fullStr Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells
title_full_unstemmed Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells
title_short Interaction of Cationic Carbosilane Dendrimers and Their siRNA Complexes with MCF-7 Cells
title_sort interaction of cationic carbosilane dendrimers and their sirna complexes with mcf 7 cells
topic siRNA
carbosilane dendrimers
dendriplexes
nanocarriers
url https://www.mdpi.com/1422-0067/22/13/7097
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