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Amphiphilic Triazine-Phosphorus Metallodendrons Possessing Anti-Cancer Stem Cell Activity

Dendritic molecules bearing metal complexes in their structure (metallodendrimers and metallodendrons) are considered prospective therapeutic entities. In particular, metallodendrons raise interest as antitumor agents for the treatment of poorly curable or drug-resistant tumors. Herein, we have synt...

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Autores principales: Apartsin, Evgeny K., Knauer, Nadezhda, Kahlert, Ulf Dietrich, Caminade, Anne-Marie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880151/
https://www.ncbi.nlm.nih.gov/pubmed/35214126
http://dx.doi.org/10.3390/pharmaceutics14020393
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author Apartsin, Evgeny K.
Knauer, Nadezhda
Kahlert, Ulf Dietrich
Caminade, Anne-Marie
author_facet Apartsin, Evgeny K.
Knauer, Nadezhda
Kahlert, Ulf Dietrich
Caminade, Anne-Marie
author_sort Apartsin, Evgeny K.
collection PubMed
description Dendritic molecules bearing metal complexes in their structure (metallodendrimers and metallodendrons) are considered prospective therapeutic entities. In particular, metallodendrons raise interest as antitumor agents for the treatment of poorly curable or drug-resistant tumors. Herein, we have synthesized amphiphilic triazine-phosphorus dendrons bearing multiple copper (II) or gold (III) complexes on the periphery and a branched hydrophobic fragment at the focal point. Due to their amphiphilic nature, metallodendrons formed single micelles (mean diameter ~9 nm) or multi-micellar aggregates (mean diameter ~60 nm) in a water solution. We have tested the antitumor activity of amphiphilic metallodendrons towards glioblastoma, a malignant brain tumor with a notoriously high level of therapy resistance, as a model disease. The metallodendrons exhibit higher cytotoxic activity towards glioblastoma stem cells (BTSC233, JHH520, NCH644, and SF188 cell lines) and U87 glioblastoma cells (IC50 was 3–6 µM for copper-containing dendron and 11–15 µM for gold-containing dendron) in comparison with temozolomide (IC50 >100 µM)—the clinical standard of care for glioblastoma. Our findings show the potential of metallodendron-based nanoformulations as antitumor entities.
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spelling pubmed-88801512022-02-26 Amphiphilic Triazine-Phosphorus Metallodendrons Possessing Anti-Cancer Stem Cell Activity Apartsin, Evgeny K. Knauer, Nadezhda Kahlert, Ulf Dietrich Caminade, Anne-Marie Pharmaceutics Article Dendritic molecules bearing metal complexes in their structure (metallodendrimers and metallodendrons) are considered prospective therapeutic entities. In particular, metallodendrons raise interest as antitumor agents for the treatment of poorly curable or drug-resistant tumors. Herein, we have synthesized amphiphilic triazine-phosphorus dendrons bearing multiple copper (II) or gold (III) complexes on the periphery and a branched hydrophobic fragment at the focal point. Due to their amphiphilic nature, metallodendrons formed single micelles (mean diameter ~9 nm) or multi-micellar aggregates (mean diameter ~60 nm) in a water solution. We have tested the antitumor activity of amphiphilic metallodendrons towards glioblastoma, a malignant brain tumor with a notoriously high level of therapy resistance, as a model disease. The metallodendrons exhibit higher cytotoxic activity towards glioblastoma stem cells (BTSC233, JHH520, NCH644, and SF188 cell lines) and U87 glioblastoma cells (IC50 was 3–6 µM for copper-containing dendron and 11–15 µM for gold-containing dendron) in comparison with temozolomide (IC50 >100 µM)—the clinical standard of care for glioblastoma. Our findings show the potential of metallodendron-based nanoformulations as antitumor entities. MDPI 2022-02-10 /pmc/articles/PMC8880151/ /pubmed/35214126 http://dx.doi.org/10.3390/pharmaceutics14020393 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Apartsin, Evgeny K.
Knauer, Nadezhda
Kahlert, Ulf Dietrich
Caminade, Anne-Marie
Amphiphilic Triazine-Phosphorus Metallodendrons Possessing Anti-Cancer Stem Cell Activity
title Amphiphilic Triazine-Phosphorus Metallodendrons Possessing Anti-Cancer Stem Cell Activity
title_full Amphiphilic Triazine-Phosphorus Metallodendrons Possessing Anti-Cancer Stem Cell Activity
title_fullStr Amphiphilic Triazine-Phosphorus Metallodendrons Possessing Anti-Cancer Stem Cell Activity
title_full_unstemmed Amphiphilic Triazine-Phosphorus Metallodendrons Possessing Anti-Cancer Stem Cell Activity
title_short Amphiphilic Triazine-Phosphorus Metallodendrons Possessing Anti-Cancer Stem Cell Activity
title_sort amphiphilic triazine-phosphorus metallodendrons possessing anti-cancer stem cell activity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880151/
https://www.ncbi.nlm.nih.gov/pubmed/35214126
http://dx.doi.org/10.3390/pharmaceutics14020393
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