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An intramolecular photoswitch can significantly promote photoactivation of Pt(iv) prodrugs
Selective activation of prodrugs at diseased tissue through bioorthogonal catalysis represents an attractive strategy for precision cancer treatment. Achieving efficient prodrug photoactivation in cancer cells, however, remains challenging. Herein, we report two Pt(iv) complexes, designated as rhoda...
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/PMC8139284/ https://www.ncbi.nlm.nih.gov/pubmed/34040729 http://dx.doi.org/10.1039/d0sc06839j |
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author | Deng, Zhiqin Li, Cai Chen, Shu Zhou, Qiyuan Xu, Zoufeng Wang, Zhigang Yao, Houzong Hirao, Hajime Zhu, Guangyu |
author_facet | Deng, Zhiqin Li, Cai Chen, Shu Zhou, Qiyuan Xu, Zoufeng Wang, Zhigang Yao, Houzong Hirao, Hajime Zhu, Guangyu |
author_sort | Deng, Zhiqin |
collection | PubMed |
description | Selective activation of prodrugs at diseased tissue through bioorthogonal catalysis represents an attractive strategy for precision cancer treatment. Achieving efficient prodrug photoactivation in cancer cells, however, remains challenging. Herein, we report two Pt(iv) complexes, designated as rhodaplatins {rhodaplatin 1, [Pt(CBDCA-O,O)(NH(3))(2)(RhB)OH]; rhodaplatin 2, [Pt(DACH)ox(RhB)(OH)], where CBDCA is cyclobutane-1,1-dicarboxylate, RhB is rhodamine B, DACH is (1R,2R)-1,2-diaminocyclohexane, and ox is oxalate}, that bear an internal photoswitch to realize efficient accumulation, significant co-localization, and subsequent effective photoactivation in cancer cells. Compared with the conventional platform of external photocatalyst plus substrate, rhodaplatins presented up to 4.8 10(4)-fold increased photoconversion efficiency in converting inert Pt(iv) prodrugs to active Pt(ii) species under physiological conditions, due to the increased proximity and covalent bond between the photoswitch and Pt(iv) substrate. As a result, rhodaplatins displayed increased photocytotoxicity compared with a mixture of RhB and conventional Pt(iv) compound in cancer cells including Pt-resistant ones. Intriguingly, rhodaplatin 2 efficiently accumulated in the mitochondria and induced apoptosis without causing genomic DNA damage to overcome drug resistance. This work presents a new approach to develop highly effective prodrugs containing intramolecular photoswitches for potential medical applications. |
format | Online Article Text |
id | pubmed-8139284 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-81392842021-05-25 An intramolecular photoswitch can significantly promote photoactivation of Pt(iv) prodrugs Deng, Zhiqin Li, Cai Chen, Shu Zhou, Qiyuan Xu, Zoufeng Wang, Zhigang Yao, Houzong Hirao, Hajime Zhu, Guangyu Chem Sci Chemistry Selective activation of prodrugs at diseased tissue through bioorthogonal catalysis represents an attractive strategy for precision cancer treatment. Achieving efficient prodrug photoactivation in cancer cells, however, remains challenging. Herein, we report two Pt(iv) complexes, designated as rhodaplatins {rhodaplatin 1, [Pt(CBDCA-O,O)(NH(3))(2)(RhB)OH]; rhodaplatin 2, [Pt(DACH)ox(RhB)(OH)], where CBDCA is cyclobutane-1,1-dicarboxylate, RhB is rhodamine B, DACH is (1R,2R)-1,2-diaminocyclohexane, and ox is oxalate}, that bear an internal photoswitch to realize efficient accumulation, significant co-localization, and subsequent effective photoactivation in cancer cells. Compared with the conventional platform of external photocatalyst plus substrate, rhodaplatins presented up to 4.8 10(4)-fold increased photoconversion efficiency in converting inert Pt(iv) prodrugs to active Pt(ii) species under physiological conditions, due to the increased proximity and covalent bond between the photoswitch and Pt(iv) substrate. As a result, rhodaplatins displayed increased photocytotoxicity compared with a mixture of RhB and conventional Pt(iv) compound in cancer cells including Pt-resistant ones. Intriguingly, rhodaplatin 2 efficiently accumulated in the mitochondria and induced apoptosis without causing genomic DNA damage to overcome drug resistance. This work presents a new approach to develop highly effective prodrugs containing intramolecular photoswitches for potential medical applications. The Royal Society of Chemistry 2021-04-01 /pmc/articles/PMC8139284/ /pubmed/34040729 http://dx.doi.org/10.1039/d0sc06839j Text en This journal is The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Deng, Zhiqin Li, Cai Chen, Shu Zhou, Qiyuan Xu, Zoufeng Wang, Zhigang Yao, Houzong Hirao, Hajime Zhu, Guangyu An intramolecular photoswitch can significantly promote photoactivation of Pt(iv) prodrugs |
title | An intramolecular photoswitch can significantly promote photoactivation of Pt(iv) prodrugs |
title_full | An intramolecular photoswitch can significantly promote photoactivation of Pt(iv) prodrugs |
title_fullStr | An intramolecular photoswitch can significantly promote photoactivation of Pt(iv) prodrugs |
title_full_unstemmed | An intramolecular photoswitch can significantly promote photoactivation of Pt(iv) prodrugs |
title_short | An intramolecular photoswitch can significantly promote photoactivation of Pt(iv) prodrugs |
title_sort | intramolecular photoswitch can significantly promote photoactivation of pt(iv) prodrugs |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139284/ https://www.ncbi.nlm.nih.gov/pubmed/34040729 http://dx.doi.org/10.1039/d0sc06839j |
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