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Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity
Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulf...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023610/ https://www.ncbi.nlm.nih.gov/pubmed/31892144 http://dx.doi.org/10.3390/polym12010043 |
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author | Andrgie, Abegaz Tizazu Birhan, Yihenew Simegniew Mekonnen, Tefera Worku Hanurry, Endiries Yibru Darge, Haile Fentahun Lee, Rong-Ho Chou, Hsiao-Ying Tsai, Hsieh-Chih |
author_facet | Andrgie, Abegaz Tizazu Birhan, Yihenew Simegniew Mekonnen, Tefera Worku Hanurry, Endiries Yibru Darge, Haile Fentahun Lee, Rong-Ho Chou, Hsiao-Ying Tsai, Hsieh-Chih |
author_sort | Andrgie, Abegaz Tizazu |
collection | PubMed |
description | Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulfide bond-containing amphiphilic heparin–chlorambucil conjugated polymeric prodrugs were designed and synthesized to enhance anti-tumor activities of chlorambucil. The conjugated prodrug could be self-assembled to form spherical vesicles with 61.33% chlorambucil grafting efficiency. The cell viability test results showed that the prodrug was biocompatible with normal cells (HaCaT) and that it selectively killed tumor cells (HeLa cells). The uptake of prodrugs by HeLa cells increased with time. Therefore, the designed prodrugs can be a better alternative as delivery vehicles for the chlorambucil controlled release in cancer cells. |
format | Online Article Text |
id | pubmed-7023610 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70236102020-03-11 Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity Andrgie, Abegaz Tizazu Birhan, Yihenew Simegniew Mekonnen, Tefera Worku Hanurry, Endiries Yibru Darge, Haile Fentahun Lee, Rong-Ho Chou, Hsiao-Ying Tsai, Hsieh-Chih Polymers (Basel) Article Polymeric prodrug-based delivery systems have been extensively studied to find a better solution for the limitations of a single drug and to improve the therapeutic and pharmacodynamics properties of chemotherapeutic agents, which can lead to efficient therapy. In this study, redox-responsive disulfide bond-containing amphiphilic heparin–chlorambucil conjugated polymeric prodrugs were designed and synthesized to enhance anti-tumor activities of chlorambucil. The conjugated prodrug could be self-assembled to form spherical vesicles with 61.33% chlorambucil grafting efficiency. The cell viability test results showed that the prodrug was biocompatible with normal cells (HaCaT) and that it selectively killed tumor cells (HeLa cells). The uptake of prodrugs by HeLa cells increased with time. Therefore, the designed prodrugs can be a better alternative as delivery vehicles for the chlorambucil controlled release in cancer cells. MDPI 2019-12-27 /pmc/articles/PMC7023610/ /pubmed/31892144 http://dx.doi.org/10.3390/polym12010043 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Andrgie, Abegaz Tizazu Birhan, Yihenew Simegniew Mekonnen, Tefera Worku Hanurry, Endiries Yibru Darge, Haile Fentahun Lee, Rong-Ho Chou, Hsiao-Ying Tsai, Hsieh-Chih Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity |
title | Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity |
title_full | Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity |
title_fullStr | Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity |
title_full_unstemmed | Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity |
title_short | Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity |
title_sort | redox-responsive heparin–chlorambucil conjugate polymeric prodrug for improved anti-tumor activity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023610/ https://www.ncbi.nlm.nih.gov/pubmed/31892144 http://dx.doi.org/10.3390/polym12010043 |
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