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...

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Main Authors:	Abegaz Tizazu Andrgie, Yihenew Simegniew Birhan, Tefera Worku Mekonnen, Endiries Yibru Hanurry, Haile Fentahun Darge, Rong-Ho Lee, Hsiao-Ying Chou, Hsieh-Chih Tsai
Format:	Article
Language:	English
Published:	MDPI AG 2019-12-01
Series:	Polymers
Subjects:	chlorambucil combination chemotherapy heparin prodrug self-assembly
Online Access:	https://www.mdpi.com/2073-4360/12/1/43

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spelling	doaj-2d90ac400d0f431ba36fa747a2e8c6302020-11-25T02:19:36ZengMDPI AGPolymers2073-43602019-12-011214310.3390/polym12010043polym12010043Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor ActivityAbegaz Tizazu Andrgie0Yihenew Simegniew Birhan1Tefera Worku Mekonnen2Endiries Yibru Hanurry3Haile Fentahun Darge4Rong-Ho Lee5Hsiao-Ying Chou6Hsieh-Chih Tsai7Graduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, TaiwanGraduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, TaiwanGraduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, TaiwanGraduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, TaiwanGraduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, TaiwanDepartment of Chemical Engineering, National Chung Hsing University, Taichung 402, TaiwanGraduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, TaiwanGraduate Institute of Applied Science and Technology, National Taiwan University of Science and Technology, Taipei 106, TaiwanPolymeric 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.https://www.mdpi.com/2073-4360/12/1/43chlorambucilcombination chemotherapyheparinprodrugself-assembly
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Abegaz Tizazu Andrgie Yihenew Simegniew Birhan Tefera Worku Mekonnen Endiries Yibru Hanurry Haile Fentahun Darge Rong-Ho Lee Hsiao-Ying Chou Hsieh-Chih Tsai
spellingShingle	Abegaz Tizazu Andrgie Yihenew Simegniew Birhan Tefera Worku Mekonnen Endiries Yibru Hanurry Haile Fentahun Darge Rong-Ho Lee Hsiao-Ying Chou Hsieh-Chih Tsai Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity Polymers chlorambucil combination chemotherapy heparin prodrug self-assembly
author_facet	Abegaz Tizazu Andrgie Yihenew Simegniew Birhan Tefera Worku Mekonnen Endiries Yibru Hanurry Haile Fentahun Darge Rong-Ho Lee Hsiao-Ying Chou Hsieh-Chih Tsai
author_sort	Abegaz Tizazu Andrgie
title	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_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_sort	redox-responsive heparin–chlorambucil conjugate polymeric prodrug for improved anti-tumor activity
publisher	MDPI AG
series	Polymers
issn	2073-4360
publishDate	2019-12-01
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.
topic	chlorambucil combination chemotherapy heparin prodrug self-assembly
url	https://www.mdpi.com/2073-4360/12/1/43
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Redox-Responsive Heparin–Chlorambucil Conjugate Polymeric Prodrug for Improved Anti-Tumor Activity

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