Dual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy

Yue Yang,1 Yunjian Li,1 Kai Chen,1 Ling Zhang,2 Sen Qiao,1 Guoxin Tan,1 Fen Chen,1,3,4 Weisan Pan1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 2Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of Ch...

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Autores principales:	Yang Y, Li Y, Chen K, Zhang L, Qiao S, Tan G, Chen F, Pan W
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	micelles paclitaxel dual-targeted redox-sensitive cytotoxicity antitumor Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/479d529428b64bb8a5c7b57748bbc460
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spelling	oai:doaj.org-article:479d529428b64bb8a5c7b57748bbc4602021-12-02T15:19:54ZDual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy1178-2013https://doaj.org/article/479d529428b64bb8a5c7b57748bbc4602020-04-01T00:00:00Zhttps://www.dovepress.com/dual-receptor-targeted-and-redox-sensitive-polymeric-micelles-self-ass-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yue Yang,1 Yunjian Li,1 Kai Chen,1 Ling Zhang,2 Sen Qiao,1 Guoxin Tan,1 Fen Chen,1,3,4 Weisan Pan1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 2Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 3Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, People’s Republic of China; 4Zhejiang Jingxin Pharmaceutical Co., Ltd, Zhejiang 312500, People’s Republic of ChinaCorrespondence: Weisan PanSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of ChinaTel/ Fax +86 24 4352 0533Email pppwwwsss@163.comFen ChenKey Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, People’s Republic of ChinaTel/ Fax +86 24 3120 7125Email chenfen1121@163.comPurpose: Poor site-specific delivery and insufficient intracellular drug release in tumors are inherent disadvantages to successful chemotherapy. In this study, an extraordinary polymeric micelle nanoplatform was designed for the efficient delivery of paclitaxel (PTX) by combining dual receptor-mediated active targeting and stimuli response to intracellular reduction potential.Methods: The dual-targeted redox-sensitive polymer, folic acid-hyaluronic acid-SS-vitamin E succinate (FHSV), was synthesized via an amidation reaction and characterized by 1H-NMR. Then, PTX-loaded FHSV micelles (PTX/FHSV) were prepared by a dialysis method. The physiochemical properties of the micelles were explored. Moreover, in vitro cytological experiments and in vivo animal studies were carried out to evaluate the antitumor efficacy of polymeric micelles.Results: The PTX/FHSV micelles exhibited a uniform, near-spherical morphology (148.8 ± 1.4 nm) and a high drug loading capacity (11.28% ± 0.25). Triggered by the high concentration of glutathione, PTX/FHSV micelles could quickly release their loaded drug into the release medium. The in vitro cytological evaluations showed that, compared with Taxol or single receptor-targeted micelles, FHSV micelles yielded higher cellular uptake by the dual receptor-mediated endocytosis pathway, thus leading to significantly superior cytotoxicity and apoptosis in tumor cells but less cytotoxicity in normal cells. More importantly, in the in vivo antitumor experiments, PTX/FHSV micelles exhibited enhanced tumor accumulation and produced remarkable tumor growth inhibition with minimal systemic toxicity.Conclusion: Our results suggest that this well-designed FHSV polymer has promising potential for use as a vehicle of chemotherapeutic drugs for precise cancer therapy.Keywords: micelles, paclitaxel, dual-targeted, redox-sensitive, cytotoxicity, antitumorYang YLi YChen KZhang LQiao STan GChen FPan WDove Medical Pressarticlemicellespaclitaxeldual-targetedredox-sensitivecytotoxicityantitumorMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 2885-2902 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	micelles paclitaxel dual-targeted redox-sensitive cytotoxicity antitumor Medicine (General) R5-920
spellingShingle	micelles paclitaxel dual-targeted redox-sensitive cytotoxicity antitumor Medicine (General) R5-920 Yang Y Li Y Chen K Zhang L Qiao S Tan G Chen F Pan W Dual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy
description	Yue Yang,1 Yunjian Li,1 Kai Chen,1 Ling Zhang,2 Sen Qiao,1 Guoxin Tan,1 Fen Chen,1,3,4 Weisan Pan1 1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of China; 2Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 3Key Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, People’s Republic of China; 4Zhejiang Jingxin Pharmaceutical Co., Ltd, Zhejiang 312500, People’s Republic of ChinaCorrespondence: Weisan PanSchool of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, People’s Republic of ChinaTel/ Fax +86 24 4352 0533Email pppwwwsss@163.comFen ChenKey Laboratory of Ministry of Education for TCM Viscera-State Theory and Applications, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, People’s Republic of ChinaTel/ Fax +86 24 3120 7125Email chenfen1121@163.comPurpose: Poor site-specific delivery and insufficient intracellular drug release in tumors are inherent disadvantages to successful chemotherapy. In this study, an extraordinary polymeric micelle nanoplatform was designed for the efficient delivery of paclitaxel (PTX) by combining dual receptor-mediated active targeting and stimuli response to intracellular reduction potential.Methods: The dual-targeted redox-sensitive polymer, folic acid-hyaluronic acid-SS-vitamin E succinate (FHSV), was synthesized via an amidation reaction and characterized by 1H-NMR. Then, PTX-loaded FHSV micelles (PTX/FHSV) were prepared by a dialysis method. The physiochemical properties of the micelles were explored. Moreover, in vitro cytological experiments and in vivo animal studies were carried out to evaluate the antitumor efficacy of polymeric micelles.Results: The PTX/FHSV micelles exhibited a uniform, near-spherical morphology (148.8 ± 1.4 nm) and a high drug loading capacity (11.28% ± 0.25). Triggered by the high concentration of glutathione, PTX/FHSV micelles could quickly release their loaded drug into the release medium. The in vitro cytological evaluations showed that, compared with Taxol or single receptor-targeted micelles, FHSV micelles yielded higher cellular uptake by the dual receptor-mediated endocytosis pathway, thus leading to significantly superior cytotoxicity and apoptosis in tumor cells but less cytotoxicity in normal cells. More importantly, in the in vivo antitumor experiments, PTX/FHSV micelles exhibited enhanced tumor accumulation and produced remarkable tumor growth inhibition with minimal systemic toxicity.Conclusion: Our results suggest that this well-designed FHSV polymer has promising potential for use as a vehicle of chemotherapeutic drugs for precise cancer therapy.Keywords: micelles, paclitaxel, dual-targeted, redox-sensitive, cytotoxicity, antitumor
format	article
author	Yang Y Li Y Chen K Zhang L Qiao S Tan G Chen F Pan W
author_facet	Yang Y Li Y Chen K Zhang L Qiao S Tan G Chen F Pan W
author_sort	Yang Y
title	Dual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy
title_short	Dual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy
title_full	Dual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy
title_fullStr	Dual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy
title_full_unstemmed	Dual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy
title_sort	dual receptor-targeted and redox-sensitive polymeric micelles self-assembled from a folic acid-hyaluronic acid-ss-vitamin e succinate polymer for precise cancer therapy
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/479d529428b64bb8a5c7b57748bbc460
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Dual Receptor-Targeted and Redox-Sensitive Polymeric Micelles Self-Assembled from a Folic Acid-Hyaluronic Acid-SS-Vitamin E Succinate Polymer for Precise Cancer Therapy

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