Doxorubicin-Bound Hydroxyethyl Starch Conjugate Nanoparticles with pH/Redox Responsive Linkage for Enhancing Antitumor Therapy

Ronghua Tan, Danlei Tian, Jiaoyan Liu, Congcong Wang, Ying Wan National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, People’s Republic of ChinaCorrespondence: Ying Wan Tel +86 27-87792147Fax +86 27...

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Autores principales:	Tan R, Tian D, Liu J, Wang C, Wan Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	hydroxyethyl starch doxorubicin conjugate nanoparticles ph/redox responsive linkage antitumor therapy Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/4b07a363284b46cdad6b81e19a33b8d0
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spelling	oai:doaj.org-article:4b07a363284b46cdad6b81e19a33b8d02021-12-02T15:06:13ZDoxorubicin-Bound Hydroxyethyl Starch Conjugate Nanoparticles with pH/Redox Responsive Linkage for Enhancing Antitumor Therapy1178-2013https://doaj.org/article/4b07a363284b46cdad6b81e19a33b8d02021-07-01T00:00:00Zhttps://www.dovepress.com/doxorubicin-bound-hydroxyethyl-starch-conjugate-nanoparticles-with-phr-peer-reviewed-fulltext-article-IJNhttps://doaj.org/toc/1178-2013Ronghua Tan, Danlei Tian, Jiaoyan Liu, Congcong Wang, Ying Wan National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, People’s Republic of ChinaCorrespondence: Ying Wan Tel +86 27-87792147Fax +86 27-87792234Email ying_wan@hust.edu.cnBackground: Chemotherapeutic drugs used for tumor treatments often show limited efficiency due to their short lifetime, nonspecific delivery, and slow or insufficient intracellular drug release, and also, they can cause severe system or organ toxicity. The development of chemotherapeutic nanomedicines with high efficacy and satisfactory safety still remains a challenge for current tumor chemotherapy.Methods: A novel type of conjugate was synthesized using hydroxyethyl starch (HES) as a carrier while binding doxorubicin (DOX) onto HES backbone through a pH/redox responsive linker containing both disulfide and hydrazone bonds in series. The built conjugates were self-assembled into nanoparticles (NPs) (HES-SS-hyd-DOX NPs) for achieving enhanced antitumor therapy and adequate safety.Results: HES-SS-hyd-DOX NPs had a certain ability for the tumor-orientated drug accumulation and were capable of releasing DOX itself rather than DOX derivatives. It was found that the pH/redox responsive linkage enabled the NPs to achieve fast and sufficient intracellular drug release. Based on the tumor-bearing mouse model, antitumor results demonstrated that these NPs were able to inhibit the growth of the advanced tumors with significantly enhanced efficacy when compared to free DOX, and to those conjugate NPs containing only a single responsive or unresponsive bond. Besides, HES-SS-hyd-DOX NPs also showed adequate safety to the normal organs of the treated mice.Conclusion: The pH/redox responsive linkage in HES-SS-hyd-DOX was found to play a critical role in mediating the drug accumulation and the fast and sufficient intracellular drug release. The HES-exposed surface of HES-SS-hyd-DOX NPs endowed the NPs with long circulation capability and remarkably reduced the DOX-induced side effects.Keywords: hydroxyethyl starch, doxorubicin, conjugate nanoparticles, pH/redox responsive linkage, antitumor therapyTan RTian DLiu JWang CWan YDove Medical Pressarticlehydroxyethyl starchdoxorubicinconjugate nanoparticlesph/redox responsive linkageantitumor therapyMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 16, Pp 4527-4544 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	hydroxyethyl starch doxorubicin conjugate nanoparticles ph/redox responsive linkage antitumor therapy Medicine (General) R5-920
spellingShingle	hydroxyethyl starch doxorubicin conjugate nanoparticles ph/redox responsive linkage antitumor therapy Medicine (General) R5-920 Tan R Tian D Liu J Wang C Wan Y Doxorubicin-Bound Hydroxyethyl Starch Conjugate Nanoparticles with pH/Redox Responsive Linkage for Enhancing Antitumor Therapy
description	Ronghua Tan, Danlei Tian, Jiaoyan Liu, Congcong Wang, Ying Wan National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, People’s Republic of ChinaCorrespondence: Ying Wan Tel +86 27-87792147Fax +86 27-87792234Email ying_wan@hust.edu.cnBackground: Chemotherapeutic drugs used for tumor treatments often show limited efficiency due to their short lifetime, nonspecific delivery, and slow or insufficient intracellular drug release, and also, they can cause severe system or organ toxicity. The development of chemotherapeutic nanomedicines with high efficacy and satisfactory safety still remains a challenge for current tumor chemotherapy.Methods: A novel type of conjugate was synthesized using hydroxyethyl starch (HES) as a carrier while binding doxorubicin (DOX) onto HES backbone through a pH/redox responsive linker containing both disulfide and hydrazone bonds in series. The built conjugates were self-assembled into nanoparticles (NPs) (HES-SS-hyd-DOX NPs) for achieving enhanced antitumor therapy and adequate safety.Results: HES-SS-hyd-DOX NPs had a certain ability for the tumor-orientated drug accumulation and were capable of releasing DOX itself rather than DOX derivatives. It was found that the pH/redox responsive linkage enabled the NPs to achieve fast and sufficient intracellular drug release. Based on the tumor-bearing mouse model, antitumor results demonstrated that these NPs were able to inhibit the growth of the advanced tumors with significantly enhanced efficacy when compared to free DOX, and to those conjugate NPs containing only a single responsive or unresponsive bond. Besides, HES-SS-hyd-DOX NPs also showed adequate safety to the normal organs of the treated mice.Conclusion: The pH/redox responsive linkage in HES-SS-hyd-DOX was found to play a critical role in mediating the drug accumulation and the fast and sufficient intracellular drug release. The HES-exposed surface of HES-SS-hyd-DOX NPs endowed the NPs with long circulation capability and remarkably reduced the DOX-induced side effects.Keywords: hydroxyethyl starch, doxorubicin, conjugate nanoparticles, pH/redox responsive linkage, antitumor therapy
format	article
author	Tan R Tian D Liu J Wang C Wan Y
author_facet	Tan R Tian D Liu J Wang C Wan Y
author_sort	Tan R
title	Doxorubicin-Bound Hydroxyethyl Starch Conjugate Nanoparticles with pH/Redox Responsive Linkage for Enhancing Antitumor Therapy
title_short	Doxorubicin-Bound Hydroxyethyl Starch Conjugate Nanoparticles with pH/Redox Responsive Linkage for Enhancing Antitumor Therapy
title_full	Doxorubicin-Bound Hydroxyethyl Starch Conjugate Nanoparticles with pH/Redox Responsive Linkage for Enhancing Antitumor Therapy
title_fullStr	Doxorubicin-Bound Hydroxyethyl Starch Conjugate Nanoparticles with pH/Redox Responsive Linkage for Enhancing Antitumor Therapy
title_full_unstemmed	Doxorubicin-Bound Hydroxyethyl Starch Conjugate Nanoparticles with pH/Redox Responsive Linkage for Enhancing Antitumor Therapy
title_sort	doxorubicin-bound hydroxyethyl starch conjugate nanoparticles with ph/redox responsive linkage for enhancing antitumor therapy
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/4b07a363284b46cdad6b81e19a33b8d0
work_keys_str_mv	AT tanr doxorubicinboundhydroxyethylstarchconjugatenanoparticleswithphredoxresponsivelinkageforenhancingantitumortherapy AT tiand doxorubicinboundhydroxyethylstarchconjugatenanoparticleswithphredoxresponsivelinkageforenhancingantitumortherapy AT liuj doxorubicinboundhydroxyethylstarchconjugatenanoparticleswithphredoxresponsivelinkageforenhancingantitumortherapy AT wangc doxorubicinboundhydroxyethylstarchconjugatenanoparticleswithphredoxresponsivelinkageforenhancingantitumortherapy AT wany doxorubicinboundhydroxyethylstarchconjugatenanoparticleswithphredoxresponsivelinkageforenhancingantitumortherapy
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Doxorubicin-Bound Hydroxyethyl Starch Conjugate Nanoparticles with pH/Redox Responsive Linkage for Enhancing Antitumor Therapy

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