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Developing an anticancer copper(II) pro-drug based on the nature of cancer cell and human serum albumin carrier IIA subdomain: mouse model of breast cancer
Human serum albumin (HSA)-based drug delivery systems are promising for improving delivery efficiency, anticancer activity and selectivity of anticancer agents. To rationally guide to design HSA carrier for anticancer metal agent, we built a breast mouse model on developing anti-cancer copper (Cu) p...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341853/ https://www.ncbi.nlm.nih.gov/pubmed/27564255 http://dx.doi.org/10.18632/oncotarget.11465 |
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author | Gou, Yi Zhang, Yao Qi, Jinxu Chen, Shifang Zhou, Zuping Wu, Xiaoyang Liang, Hong Yang, Feng |
author_facet | Gou, Yi Zhang, Yao Qi, Jinxu Chen, Shifang Zhou, Zuping Wu, Xiaoyang Liang, Hong Yang, Feng |
author_sort | Gou, Yi |
collection | PubMed |
description | Human serum albumin (HSA)-based drug delivery systems are promising for improving delivery efficiency, anticancer activity and selectivity of anticancer agents. To rationally guide to design HSA carrier for anticancer metal agent, we built a breast mouse model on developing anti-cancer copper (Cu) pro-drug based on the nature of IIA subdomain of HSA carrier and cancer cells. Thus, we first synthesized a new Cu(II) compound derived from tridentate (E)-N'-(5-bromo-2-hydroxybenzylidene)benzohydrazide Schiff base ligand (HL) containing 2 potential leaving groups [indazole (Ind) and NO(3)(−)], namely, [Cu(L)(Ind)NO(3)]. Structural analysis of the HSA complex showed that Cu(L)(Ind)(NO(3)) could bind to the hydrophobic pocket of the HSA IIA subdomain. Lys199 and His242 coordinate with Cu(2+) by replacing the indazole and NO(3) ligands of [Cu(L)(Ind)NO(3)]. The release behavior of the Cu compound from the HSA complex is different at different pH levels. [Cu(L)(Ind)NO(3)] can enhance cytotoxicity by 2 times together with HSA specifically in cancer cells but has no such effect on normal cells in vitro. Importantly, our in vivo results showed that the HSA complex displayed increased selectivity and capacity to inhibit tumor growth and was less toxic than [Cu(L)(Ind)NO(3)] alone. |
format | Online Article Text |
id | pubmed-5341853 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-53418532017-03-23 Developing an anticancer copper(II) pro-drug based on the nature of cancer cell and human serum albumin carrier IIA subdomain: mouse model of breast cancer Gou, Yi Zhang, Yao Qi, Jinxu Chen, Shifang Zhou, Zuping Wu, Xiaoyang Liang, Hong Yang, Feng Oncotarget Research Paper Human serum albumin (HSA)-based drug delivery systems are promising for improving delivery efficiency, anticancer activity and selectivity of anticancer agents. To rationally guide to design HSA carrier for anticancer metal agent, we built a breast mouse model on developing anti-cancer copper (Cu) pro-drug based on the nature of IIA subdomain of HSA carrier and cancer cells. Thus, we first synthesized a new Cu(II) compound derived from tridentate (E)-N'-(5-bromo-2-hydroxybenzylidene)benzohydrazide Schiff base ligand (HL) containing 2 potential leaving groups [indazole (Ind) and NO(3)(−)], namely, [Cu(L)(Ind)NO(3)]. Structural analysis of the HSA complex showed that Cu(L)(Ind)(NO(3)) could bind to the hydrophobic pocket of the HSA IIA subdomain. Lys199 and His242 coordinate with Cu(2+) by replacing the indazole and NO(3) ligands of [Cu(L)(Ind)NO(3)]. The release behavior of the Cu compound from the HSA complex is different at different pH levels. [Cu(L)(Ind)NO(3)] can enhance cytotoxicity by 2 times together with HSA specifically in cancer cells but has no such effect on normal cells in vitro. Importantly, our in vivo results showed that the HSA complex displayed increased selectivity and capacity to inhibit tumor growth and was less toxic than [Cu(L)(Ind)NO(3)] alone. Impact Journals LLC 2016-08-22 /pmc/articles/PMC5341853/ /pubmed/27564255 http://dx.doi.org/10.18632/oncotarget.11465 Text en Copyright: © 2016 Gou et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Gou, Yi Zhang, Yao Qi, Jinxu Chen, Shifang Zhou, Zuping Wu, Xiaoyang Liang, Hong Yang, Feng Developing an anticancer copper(II) pro-drug based on the nature of cancer cell and human serum albumin carrier IIA subdomain: mouse model of breast cancer |
title | Developing an anticancer copper(II) pro-drug based on the nature of cancer cell and human serum albumin carrier IIA subdomain: mouse model of breast cancer |
title_full | Developing an anticancer copper(II) pro-drug based on the nature of cancer cell and human serum albumin carrier IIA subdomain: mouse model of breast cancer |
title_fullStr | Developing an anticancer copper(II) pro-drug based on the nature of cancer cell and human serum albumin carrier IIA subdomain: mouse model of breast cancer |
title_full_unstemmed | Developing an anticancer copper(II) pro-drug based on the nature of cancer cell and human serum albumin carrier IIA subdomain: mouse model of breast cancer |
title_short | Developing an anticancer copper(II) pro-drug based on the nature of cancer cell and human serum albumin carrier IIA subdomain: mouse model of breast cancer |
title_sort | developing an anticancer copper(ii) pro-drug based on the nature of cancer cell and human serum albumin carrier iia subdomain: mouse model of breast cancer |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341853/ https://www.ncbi.nlm.nih.gov/pubmed/27564255 http://dx.doi.org/10.18632/oncotarget.11465 |
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