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Novel Multiarm Polyethylene glycol-Dihydroartemisinin Conjugates Enhancing Therapeutic Efficacy in Non-Small-Cell Lung Cancer
The clinical application of dihydroartemisinin (DHA) has been hampered due to its poor water-solubility. To overcome this hurdle, we devised a novel polymer-drug conjugate, multiarm polyethylene glycol-dihydroartemisinin (PEG-DHA), made by linking DHA with multiarm polyethylene glycol. Herein, we in...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376196/ https://www.ncbi.nlm.nih.gov/pubmed/25070490 http://dx.doi.org/10.1038/srep05871 |
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author | Dai, Lin Wang, Luying Deng, Lihong Liu, Jing Lei, Jiandu Li, Dan He, Jing |
author_facet | Dai, Lin Wang, Luying Deng, Lihong Liu, Jing Lei, Jiandu Li, Dan He, Jing |
author_sort | Dai, Lin |
collection | PubMed |
description | The clinical application of dihydroartemisinin (DHA) has been hampered due to its poor water-solubility. To overcome this hurdle, we devised a novel polymer-drug conjugate, multiarm polyethylene glycol-dihydroartemisinin (PEG-DHA), made by linking DHA with multiarm polyethylene glycol. Herein, we investigated PEG-DHA on chemical structure, hydrolysis, solubility, hemolysis, cell cytotoxicity in vitro, and efficacy in vivo. The PEG-DHA conjugates have showed moderate drug loadings (2.82 ~ 8.14 wt%), significantly good water-solubilities (82- ~ 163-fold of DHA), excellent in vitro anticancer activities (at concentrations ≥8 μg/ml, showed only 15–20% cell viability) with potency similar to that of native DHA, and long blood circulation half-time (5.75- ~ 16.75-fold of DHA). Subsequent tumor xenograft assays demonstrated a superior therapeutic effect of PEG-DHA on inhibition of tumor growth compared with native DHA. The novel PEG-DHA conjugates can not only improve the solubility and efficacy of DHA but also show the potential of scale-up production and clinical application. |
format | Online Article Text |
id | pubmed-5376196 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-53761962017-04-03 Novel Multiarm Polyethylene glycol-Dihydroartemisinin Conjugates Enhancing Therapeutic Efficacy in Non-Small-Cell Lung Cancer Dai, Lin Wang, Luying Deng, Lihong Liu, Jing Lei, Jiandu Li, Dan He, Jing Sci Rep Article The clinical application of dihydroartemisinin (DHA) has been hampered due to its poor water-solubility. To overcome this hurdle, we devised a novel polymer-drug conjugate, multiarm polyethylene glycol-dihydroartemisinin (PEG-DHA), made by linking DHA with multiarm polyethylene glycol. Herein, we investigated PEG-DHA on chemical structure, hydrolysis, solubility, hemolysis, cell cytotoxicity in vitro, and efficacy in vivo. The PEG-DHA conjugates have showed moderate drug loadings (2.82 ~ 8.14 wt%), significantly good water-solubilities (82- ~ 163-fold of DHA), excellent in vitro anticancer activities (at concentrations ≥8 μg/ml, showed only 15–20% cell viability) with potency similar to that of native DHA, and long blood circulation half-time (5.75- ~ 16.75-fold of DHA). Subsequent tumor xenograft assays demonstrated a superior therapeutic effect of PEG-DHA on inhibition of tumor growth compared with native DHA. The novel PEG-DHA conjugates can not only improve the solubility and efficacy of DHA but also show the potential of scale-up production and clinical application. Nature Publishing Group 2014-07-29 /pmc/articles/PMC5376196/ /pubmed/25070490 http://dx.doi.org/10.1038/srep05871 Text en Copyright © 2014, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder in order to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Dai, Lin Wang, Luying Deng, Lihong Liu, Jing Lei, Jiandu Li, Dan He, Jing Novel Multiarm Polyethylene glycol-Dihydroartemisinin Conjugates Enhancing Therapeutic Efficacy in Non-Small-Cell Lung Cancer |
title | Novel Multiarm Polyethylene glycol-Dihydroartemisinin Conjugates Enhancing Therapeutic Efficacy in Non-Small-Cell Lung Cancer |
title_full | Novel Multiarm Polyethylene glycol-Dihydroartemisinin Conjugates Enhancing Therapeutic Efficacy in Non-Small-Cell Lung Cancer |
title_fullStr | Novel Multiarm Polyethylene glycol-Dihydroartemisinin Conjugates Enhancing Therapeutic Efficacy in Non-Small-Cell Lung Cancer |
title_full_unstemmed | Novel Multiarm Polyethylene glycol-Dihydroartemisinin Conjugates Enhancing Therapeutic Efficacy in Non-Small-Cell Lung Cancer |
title_short | Novel Multiarm Polyethylene glycol-Dihydroartemisinin Conjugates Enhancing Therapeutic Efficacy in Non-Small-Cell Lung Cancer |
title_sort | novel multiarm polyethylene glycol-dihydroartemisinin conjugates enhancing therapeutic efficacy in non-small-cell lung cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5376196/ https://www.ncbi.nlm.nih.gov/pubmed/25070490 http://dx.doi.org/10.1038/srep05871 |
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