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Cell-permeable lanthanide–platinum(iv) anti-cancer prodrugs
Platinum compounds are a vital part of our anti-cancer arsenal, and determining the location and speciation of platinum compounds is crucial. We have synthesised a lanthanide complex bearing a salicylic group (Ln = Gd, Eu) which demonstrates excellent cellular accumulation and minimal cytotoxicity....
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237448/ https://www.ncbi.nlm.nih.gov/pubmed/34080595 http://dx.doi.org/10.1039/d1dt01688a |
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author | Yao, Kezi Karunanithy, Gogulan Howarth, Alison Holdship, Philip Thompson, Amber L. Christensen, Kirsten E. Baldwin, Andrew J. Faulkner, Stephen Farrer, Nicola J. |
author_facet | Yao, Kezi Karunanithy, Gogulan Howarth, Alison Holdship, Philip Thompson, Amber L. Christensen, Kirsten E. Baldwin, Andrew J. Faulkner, Stephen Farrer, Nicola J. |
author_sort | Yao, Kezi |
collection | PubMed |
description | Platinum compounds are a vital part of our anti-cancer arsenal, and determining the location and speciation of platinum compounds is crucial. We have synthesised a lanthanide complex bearing a salicylic group (Ln = Gd, Eu) which demonstrates excellent cellular accumulation and minimal cytotoxicity. Derivatisation enabled access to bimetallic lanthanide–platinum(ii) and lanthanide–platinum(iv) complexes. Luminescence from the europium–platinum(iv) system was quenched, and reduction to platinum(ii) with ascorbic acid resulted in a “switch-on” luminescence enhancement. We used diffusion-based (1)H NMR spectroscopic methods to quantify cellular accumulation. The gadolinium–platinum(ii) and gadolinium–platinum(iv) complexes demonstrated appreciable cytotoxicity. A longer delay following incubation before cytotoxicity was observed for the gadolinium–platinum(iv) compared to the gadolinium–platinum(ii) complex. Functionalisation with octanoate ligands resulted in enhanced cellular accumulation and an even greater latency in cytotoxicity. |
format | Online Article Text |
id | pubmed-8237448 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-82374482021-07-12 Cell-permeable lanthanide–platinum(iv) anti-cancer prodrugs Yao, Kezi Karunanithy, Gogulan Howarth, Alison Holdship, Philip Thompson, Amber L. Christensen, Kirsten E. Baldwin, Andrew J. Faulkner, Stephen Farrer, Nicola J. Dalton Trans Chemistry Platinum compounds are a vital part of our anti-cancer arsenal, and determining the location and speciation of platinum compounds is crucial. We have synthesised a lanthanide complex bearing a salicylic group (Ln = Gd, Eu) which demonstrates excellent cellular accumulation and minimal cytotoxicity. Derivatisation enabled access to bimetallic lanthanide–platinum(ii) and lanthanide–platinum(iv) complexes. Luminescence from the europium–platinum(iv) system was quenched, and reduction to platinum(ii) with ascorbic acid resulted in a “switch-on” luminescence enhancement. We used diffusion-based (1)H NMR spectroscopic methods to quantify cellular accumulation. The gadolinium–platinum(ii) and gadolinium–platinum(iv) complexes demonstrated appreciable cytotoxicity. A longer delay following incubation before cytotoxicity was observed for the gadolinium–platinum(iv) compared to the gadolinium–platinum(ii) complex. Functionalisation with octanoate ligands resulted in enhanced cellular accumulation and an even greater latency in cytotoxicity. The Royal Society of Chemistry 2021-05-28 /pmc/articles/PMC8237448/ /pubmed/34080595 http://dx.doi.org/10.1039/d1dt01688a Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Yao, Kezi Karunanithy, Gogulan Howarth, Alison Holdship, Philip Thompson, Amber L. Christensen, Kirsten E. Baldwin, Andrew J. Faulkner, Stephen Farrer, Nicola J. Cell-permeable lanthanide–platinum(iv) anti-cancer prodrugs |
title | Cell-permeable lanthanide–platinum(iv) anti-cancer prodrugs |
title_full | Cell-permeable lanthanide–platinum(iv) anti-cancer prodrugs |
title_fullStr | Cell-permeable lanthanide–platinum(iv) anti-cancer prodrugs |
title_full_unstemmed | Cell-permeable lanthanide–platinum(iv) anti-cancer prodrugs |
title_short | Cell-permeable lanthanide–platinum(iv) anti-cancer prodrugs |
title_sort | cell-permeable lanthanide–platinum(iv) anti-cancer prodrugs |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237448/ https://www.ncbi.nlm.nih.gov/pubmed/34080595 http://dx.doi.org/10.1039/d1dt01688a |
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