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In vitro and ex vivo anti-myeloma effects of nanocomposite As(4)S(4)/ZnS/Fe(3)O(4)
Nanoparticles in medicine can integrate actively targeted imaging agents and drug delivery vehicles, and combining multiple types of therapeutics in a single particle has numerous advantages, especially in multiple myeloma. MM is an incurable hematological disorder characterized by clonal proliferat...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606304/ https://www.ncbi.nlm.nih.gov/pubmed/36289430 http://dx.doi.org/10.1038/s41598-022-22672-5 |
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author | Cholujova, Danka Koklesova, Lenka Lukacova Bujnakova, Zdenka Dutkova, Erika Valuskova, Zuzana Beblava, Patricia Matisova, Anna Sedlak, Jan Jakubikova, Jana |
author_facet | Cholujova, Danka Koklesova, Lenka Lukacova Bujnakova, Zdenka Dutkova, Erika Valuskova, Zuzana Beblava, Patricia Matisova, Anna Sedlak, Jan Jakubikova, Jana |
author_sort | Cholujova, Danka |
collection | PubMed |
description | Nanoparticles in medicine can integrate actively targeted imaging agents and drug delivery vehicles, and combining multiple types of therapeutics in a single particle has numerous advantages, especially in multiple myeloma. MM is an incurable hematological disorder characterized by clonal proliferation of plasma cells in the bone marrow. In this study, we evaluated the anti-myeloma activity of 3 nanocomposites (3NPs): As(4)S(4)/ZnS/Fe(3)O(4) (1:4:1), As(4)S(4)/ZnS/Fe(3)O(4) with folic acid (FA), and As(4)S(4)/ZnS/Fe(3)O(4) with FA and albumin with reduced survival MM cell lines and primary MM samples by each of 3NP. Cytotoxic effects of 3NPs were associated with caspase- and mitochondria-dependent apoptosis induction and reduced c-Myc expression. Modulation of cell cycle regulators, such as p-ATM/ATM and p-ATR/ATR, and increases in p-Chk2, cyclin B1, and histones were accompanied by G(2)/M arrest triggered by 3NPs. In addition, 3NPs activated several myeloma-related signaling, including JNK1/2/3, ERK1/2 and mTOR. To overcome BM microenvironment-mediated drug resistance, nanocomposites retained its anti-MM activity in the presence of stroma. 3NPs significantly decreased the stem cell-like side population in MM cells, even in the context of stroma. We observed strong synergistic effects of 3NPs combined with lenalidomide, pomalidomide, or melphalan, suggesting the potential of these combinations for future clinical studies. |
format | Online Article Text |
id | pubmed-9606304 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-96063042022-10-28 In vitro and ex vivo anti-myeloma effects of nanocomposite As(4)S(4)/ZnS/Fe(3)O(4) Cholujova, Danka Koklesova, Lenka Lukacova Bujnakova, Zdenka Dutkova, Erika Valuskova, Zuzana Beblava, Patricia Matisova, Anna Sedlak, Jan Jakubikova, Jana Sci Rep Article Nanoparticles in medicine can integrate actively targeted imaging agents and drug delivery vehicles, and combining multiple types of therapeutics in a single particle has numerous advantages, especially in multiple myeloma. MM is an incurable hematological disorder characterized by clonal proliferation of plasma cells in the bone marrow. In this study, we evaluated the anti-myeloma activity of 3 nanocomposites (3NPs): As(4)S(4)/ZnS/Fe(3)O(4) (1:4:1), As(4)S(4)/ZnS/Fe(3)O(4) with folic acid (FA), and As(4)S(4)/ZnS/Fe(3)O(4) with FA and albumin with reduced survival MM cell lines and primary MM samples by each of 3NP. Cytotoxic effects of 3NPs were associated with caspase- and mitochondria-dependent apoptosis induction and reduced c-Myc expression. Modulation of cell cycle regulators, such as p-ATM/ATM and p-ATR/ATR, and increases in p-Chk2, cyclin B1, and histones were accompanied by G(2)/M arrest triggered by 3NPs. In addition, 3NPs activated several myeloma-related signaling, including JNK1/2/3, ERK1/2 and mTOR. To overcome BM microenvironment-mediated drug resistance, nanocomposites retained its anti-MM activity in the presence of stroma. 3NPs significantly decreased the stem cell-like side population in MM cells, even in the context of stroma. We observed strong synergistic effects of 3NPs combined with lenalidomide, pomalidomide, or melphalan, suggesting the potential of these combinations for future clinical studies. Nature Publishing Group UK 2022-10-26 /pmc/articles/PMC9606304/ /pubmed/36289430 http://dx.doi.org/10.1038/s41598-022-22672-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Cholujova, Danka Koklesova, Lenka Lukacova Bujnakova, Zdenka Dutkova, Erika Valuskova, Zuzana Beblava, Patricia Matisova, Anna Sedlak, Jan Jakubikova, Jana In vitro and ex vivo anti-myeloma effects of nanocomposite As(4)S(4)/ZnS/Fe(3)O(4) |
title | In vitro and ex vivo anti-myeloma effects of nanocomposite As(4)S(4)/ZnS/Fe(3)O(4) |
title_full | In vitro and ex vivo anti-myeloma effects of nanocomposite As(4)S(4)/ZnS/Fe(3)O(4) |
title_fullStr | In vitro and ex vivo anti-myeloma effects of nanocomposite As(4)S(4)/ZnS/Fe(3)O(4) |
title_full_unstemmed | In vitro and ex vivo anti-myeloma effects of nanocomposite As(4)S(4)/ZnS/Fe(3)O(4) |
title_short | In vitro and ex vivo anti-myeloma effects of nanocomposite As(4)S(4)/ZnS/Fe(3)O(4) |
title_sort | in vitro and ex vivo anti-myeloma effects of nanocomposite as(4)s(4)/zns/fe(3)o(4) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9606304/ https://www.ncbi.nlm.nih.gov/pubmed/36289430 http://dx.doi.org/10.1038/s41598-022-22672-5 |
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