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Hypoxia-Activated Albumin-Binding Exatecan Prodrug for Cancer Therapy
[Image: see text] As an effective drug delivery strategy for traditional antitumor drugs, the stimulus-responsive albumin-based prodrugs are getting more and more attention. These prodrugs only release drugs in specific tumor microenvironments, which can prevent premature release of the drug in the...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757358/ https://www.ncbi.nlm.nih.gov/pubmed/35036771 http://dx.doi.org/10.1021/acsomega.1c05671 |
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author | Cheng, Zhiyang Huang, Ying Shao, Pingxuan Wang, Lei Zhu, Shulei Yu, Jiahui Lu, Wei |
author_facet | Cheng, Zhiyang Huang, Ying Shao, Pingxuan Wang, Lei Zhu, Shulei Yu, Jiahui Lu, Wei |
author_sort | Cheng, Zhiyang |
collection | PubMed |
description | [Image: see text] As an effective drug delivery strategy for traditional antitumor drugs, the stimulus-responsive albumin-based prodrugs are getting more and more attention. These prodrugs only release drugs in specific tumor microenvironments, which can prevent premature release of the drug in the circulation. Tumor hypoxia is a fundamental feature of the solid tumor microenvironment. As a hypoxia-activated linker, the 5-position branched linker of 1-methyl-2-nitro-5-hydroxymethylimidazole can be a trigger for albumin-based prodrugs. In this study, we report the synthesis and biological evaluation of the hypoxia-activated albumin-binding prodrug Mal-azo-Exatecan. After intravenous administration, the maleimide on the side chain can rapidly bind to endogenous albumin, enabling the prodrugs to accumulate in tumors, where tumor-associated hypoxia microenvironments trigger the selective release of Exatecan. The 5-position branched linker of 1-methyl-2-nitro-5-hydroxymethylimidazole as a cleavable linker has high plasma stability and does not cause Exatecan release from HSA-azo-Exatecan during circulation in vivo, avoiding systemic side effects caused by Exatecan. |
format | Online Article Text |
id | pubmed-8757358 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-87573582022-01-13 Hypoxia-Activated Albumin-Binding Exatecan Prodrug for Cancer Therapy Cheng, Zhiyang Huang, Ying Shao, Pingxuan Wang, Lei Zhu, Shulei Yu, Jiahui Lu, Wei ACS Omega [Image: see text] As an effective drug delivery strategy for traditional antitumor drugs, the stimulus-responsive albumin-based prodrugs are getting more and more attention. These prodrugs only release drugs in specific tumor microenvironments, which can prevent premature release of the drug in the circulation. Tumor hypoxia is a fundamental feature of the solid tumor microenvironment. As a hypoxia-activated linker, the 5-position branched linker of 1-methyl-2-nitro-5-hydroxymethylimidazole can be a trigger for albumin-based prodrugs. In this study, we report the synthesis and biological evaluation of the hypoxia-activated albumin-binding prodrug Mal-azo-Exatecan. After intravenous administration, the maleimide on the side chain can rapidly bind to endogenous albumin, enabling the prodrugs to accumulate in tumors, where tumor-associated hypoxia microenvironments trigger the selective release of Exatecan. The 5-position branched linker of 1-methyl-2-nitro-5-hydroxymethylimidazole as a cleavable linker has high plasma stability and does not cause Exatecan release from HSA-azo-Exatecan during circulation in vivo, avoiding systemic side effects caused by Exatecan. American Chemical Society 2021-12-30 /pmc/articles/PMC8757358/ /pubmed/35036771 http://dx.doi.org/10.1021/acsomega.1c05671 Text en © 2021 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Cheng, Zhiyang Huang, Ying Shao, Pingxuan Wang, Lei Zhu, Shulei Yu, Jiahui Lu, Wei Hypoxia-Activated Albumin-Binding Exatecan Prodrug for Cancer Therapy |
title | Hypoxia-Activated Albumin-Binding Exatecan Prodrug
for Cancer Therapy |
title_full | Hypoxia-Activated Albumin-Binding Exatecan Prodrug
for Cancer Therapy |
title_fullStr | Hypoxia-Activated Albumin-Binding Exatecan Prodrug
for Cancer Therapy |
title_full_unstemmed | Hypoxia-Activated Albumin-Binding Exatecan Prodrug
for Cancer Therapy |
title_short | Hypoxia-Activated Albumin-Binding Exatecan Prodrug
for Cancer Therapy |
title_sort | hypoxia-activated albumin-binding exatecan prodrug
for cancer therapy |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8757358/ https://www.ncbi.nlm.nih.gov/pubmed/35036771 http://dx.doi.org/10.1021/acsomega.1c05671 |
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