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Surmounting tumor resistance to metallodrugs by co-loading a metal complex and siRNA in nanoparticles

Copper complexes are promising anticancer agents widely studied to overcome tumor resistance to metal-based anticancer drugs. Nevertheless, copper complexes per se encounter drug resistance from time to time. Adenosine-5′-triphosphate (ATP)-responsive nanoparticles containing a copper complex CTND a...

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Detalles Bibliográficos
Autores principales: Qiao, Hongzhi, Zhang, Lei, Fang, Dong, Zhu, Zhenzhu, He, Weijiang, Hu, Lihong, Di, Liuqing, Guo, Zijian, Wang, Xiaoyong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179575/
https://www.ncbi.nlm.nih.gov/pubmed/34163720
http://dx.doi.org/10.1039/d0sc06680j
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author Qiao, Hongzhi
Zhang, Lei
Fang, Dong
Zhu, Zhenzhu
He, Weijiang
Hu, Lihong
Di, Liuqing
Guo, Zijian
Wang, Xiaoyong
author_facet Qiao, Hongzhi
Zhang, Lei
Fang, Dong
Zhu, Zhenzhu
He, Weijiang
Hu, Lihong
Di, Liuqing
Guo, Zijian
Wang, Xiaoyong
author_sort Qiao, Hongzhi
collection PubMed
description Copper complexes are promising anticancer agents widely studied to overcome tumor resistance to metal-based anticancer drugs. Nevertheless, copper complexes per se encounter drug resistance from time to time. Adenosine-5′-triphosphate (ATP)-responsive nanoparticles containing a copper complex CTND and B-cell lymphoma 2 (Bcl-2) small interfering RNA (siRNA) were constructed to cope with the resistance of cancer cells to the complex. CTND and siRNA can be released from the nanoparticles in cancer cells upon reacting with intracellular ATP. The resistance of B16F10 melanoma cells to CTND was terminated by silencing the cellular Bcl-2 gene via RNA interference, and the therapeutic efficacy was significantly enhanced. The nanoparticles triggered a cellular autophagy that amplified the apoptotic signals, thus revealing a novel mechanism for antagonizing the resistance of copper complexes. In view of the extensive association of Bcl-2 protein with cancer resistance to chemotherapeutics, this strategy may be universally applicable for overcoming the ubiquitous drug resistance to metallodrugs.
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spelling pubmed-81795752021-06-22 Surmounting tumor resistance to metallodrugs by co-loading a metal complex and siRNA in nanoparticles Qiao, Hongzhi Zhang, Lei Fang, Dong Zhu, Zhenzhu He, Weijiang Hu, Lihong Di, Liuqing Guo, Zijian Wang, Xiaoyong Chem Sci Chemistry Copper complexes are promising anticancer agents widely studied to overcome tumor resistance to metal-based anticancer drugs. Nevertheless, copper complexes per se encounter drug resistance from time to time. Adenosine-5′-triphosphate (ATP)-responsive nanoparticles containing a copper complex CTND and B-cell lymphoma 2 (Bcl-2) small interfering RNA (siRNA) were constructed to cope with the resistance of cancer cells to the complex. CTND and siRNA can be released from the nanoparticles in cancer cells upon reacting with intracellular ATP. The resistance of B16F10 melanoma cells to CTND was terminated by silencing the cellular Bcl-2 gene via RNA interference, and the therapeutic efficacy was significantly enhanced. The nanoparticles triggered a cellular autophagy that amplified the apoptotic signals, thus revealing a novel mechanism for antagonizing the resistance of copper complexes. In view of the extensive association of Bcl-2 protein with cancer resistance to chemotherapeutics, this strategy may be universally applicable for overcoming the ubiquitous drug resistance to metallodrugs. The Royal Society of Chemistry 2021-02-09 /pmc/articles/PMC8179575/ /pubmed/34163720 http://dx.doi.org/10.1039/d0sc06680j Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/
spellingShingle Chemistry
Qiao, Hongzhi
Zhang, Lei
Fang, Dong
Zhu, Zhenzhu
He, Weijiang
Hu, Lihong
Di, Liuqing
Guo, Zijian
Wang, Xiaoyong
Surmounting tumor resistance to metallodrugs by co-loading a metal complex and siRNA in nanoparticles
title Surmounting tumor resistance to metallodrugs by co-loading a metal complex and siRNA in nanoparticles
title_full Surmounting tumor resistance to metallodrugs by co-loading a metal complex and siRNA in nanoparticles
title_fullStr Surmounting tumor resistance to metallodrugs by co-loading a metal complex and siRNA in nanoparticles
title_full_unstemmed Surmounting tumor resistance to metallodrugs by co-loading a metal complex and siRNA in nanoparticles
title_short Surmounting tumor resistance to metallodrugs by co-loading a metal complex and siRNA in nanoparticles
title_sort surmounting tumor resistance to metallodrugs by co-loading a metal complex and sirna in nanoparticles
topic Chemistry
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179575/
https://www.ncbi.nlm.nih.gov/pubmed/34163720
http://dx.doi.org/10.1039/d0sc06680j
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