Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery

Yishun Yang,1 Yuan Zhao,2 Jinshuai Lan,1 Yanan Kang,3 Tong Zhang,1 Yue Ding,1 Xinyu Zhang,1 Lu Lu3 1Experiment Centre of Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2Experiment Centre for Science and Technology, Shanghai University of Traditional Chi...

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Autores principales:	Yang YS, Zhao Y, Lan JS, Kang YN, Zhang T, Ding Y, Zhang XY, Lu L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2018
Materias:	hyaluronic acid CD44 receptor-targeting redox responsive folate micelles doxorubicin Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/77724f237d134617b9b9e6cae688df19
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spelling	oai:doaj.org-article:77724f237d134617b9b9e6cae688df192021-12-02T07:31:34ZReduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery1178-2013https://doaj.org/article/77724f237d134617b9b9e6cae688df192018-07-01T00:00:00Zhttps://www.dovepress.com/reduction-sensitive-cd44-receptor-targeted-hyaluronic-acid-derivative--peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yishun Yang,1 Yuan Zhao,2 Jinshuai Lan,1 Yanan Kang,3 Tong Zhang,1 Yue Ding,1 Xinyu Zhang,1 Lu Lu3 1Experiment Centre of Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2Experiment Centre for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 3School of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China Introduction: A reduction-sensitive CD44-positive tumor-targetable drug delivery system for doxorubicin (DOX) delivery was developed based on hyaluronic acid (HA)-grafted polymers. Materials and methods: HA was conjugated with folic acid (FA) via a reduction-sensitive disulfide linkage to form an amphiphilic polymer (HA-ss-FA). The chemical structure of HA-ss-FA was analyzed by ultraviolet spectroscopy, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance (NMR) spectroscopy. The molecular weight of HA-ss-FA was determined by high-performance gel permeation chromatography. Blank HA-ss-FA micelles and DOX-loaded micelles were prepared and characterized. The reduction responsibility, cellular uptake, and in vivo biodistribution of HA-ss-FA micelles were investigated. Results: DOX-loaded micelles were of high encapsulation efficiency (88.09%), high drug-loading content (22.70%), appropriate mean diameter (100–120 nm), narrow size distribution, and negative zeta potential (-6.7 to -31.5 mV). The DOX release from the micelles was significantly enhanced in reduction environment compared to normal environment. The result of in vitro cytotoxicity assay indicated that the blank micelles were of low toxicity and good biocompatibility and the cell viabilities were >100% with the concentration of HA-ss-FA from 18.75 to 600.00 µg/mL. Cellular uptake and in vivo biodistribution studies showed that DOX-loaded micelles were tumor-targetable and could significantly enhance cellular uptake by CD44 receptor-mediated endocytosis, and the cellular uptake of DOX in CD44-positve A549 cells was 1.6-fold more than that in CD44-negative L02 cells. In vivo biodistribution of HA-ss-FA micelles showed that micelles were of good in vivo tumor targetability and the fluorescence of indocyanine green (ICG)-loaded micelles was 4- to 6.6-fold stronger than free ICG within 6 h in HCCLM3 tumor-bearing nude mice. Conclusion: HA-ss-FA is a promising nanocarrier with excellent biocompatibility, tumor targetability, and controlled drug release capability for delivery of chemotherapy drugs in cancer therapy. Keywords: hyaluronic acid, CD44 receptor targeting, redox responsive, folic acid, micelles, doxorubicinYang YSZhao YLan JSKang YNZhang TDing YZhang XYLu LDove Medical Pressarticlehyaluronic acidCD44 receptor-targetingredox responsivefolatemicellesdoxorubicinMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 13, Pp 4361-4378 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	hyaluronic acid CD44 receptor-targeting redox responsive folate micelles doxorubicin Medicine (General) R5-920
spellingShingle	hyaluronic acid CD44 receptor-targeting redox responsive folate micelles doxorubicin Medicine (General) R5-920 Yang YS Zhao Y Lan JS Kang YN Zhang T Ding Y Zhang XY Lu L Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery
description	Yishun Yang,1 Yuan Zhao,2 Jinshuai Lan,1 Yanan Kang,3 Tong Zhang,1 Yue Ding,1 Xinyu Zhang,1 Lu Lu3 1Experiment Centre of Teaching and Learning, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 2Experiment Centre for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, China; 3School of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China Introduction: A reduction-sensitive CD44-positive tumor-targetable drug delivery system for doxorubicin (DOX) delivery was developed based on hyaluronic acid (HA)-grafted polymers. Materials and methods: HA was conjugated with folic acid (FA) via a reduction-sensitive disulfide linkage to form an amphiphilic polymer (HA-ss-FA). The chemical structure of HA-ss-FA was analyzed by ultraviolet spectroscopy, Fourier transform infrared spectroscopy, and 1H nuclear magnetic resonance (NMR) spectroscopy. The molecular weight of HA-ss-FA was determined by high-performance gel permeation chromatography. Blank HA-ss-FA micelles and DOX-loaded micelles were prepared and characterized. The reduction responsibility, cellular uptake, and in vivo biodistribution of HA-ss-FA micelles were investigated. Results: DOX-loaded micelles were of high encapsulation efficiency (88.09%), high drug-loading content (22.70%), appropriate mean diameter (100–120 nm), narrow size distribution, and negative zeta potential (-6.7 to -31.5 mV). The DOX release from the micelles was significantly enhanced in reduction environment compared to normal environment. The result of in vitro cytotoxicity assay indicated that the blank micelles were of low toxicity and good biocompatibility and the cell viabilities were >100% with the concentration of HA-ss-FA from 18.75 to 600.00 µg/mL. Cellular uptake and in vivo biodistribution studies showed that DOX-loaded micelles were tumor-targetable and could significantly enhance cellular uptake by CD44 receptor-mediated endocytosis, and the cellular uptake of DOX in CD44-positve A549 cells was 1.6-fold more than that in CD44-negative L02 cells. In vivo biodistribution of HA-ss-FA micelles showed that micelles were of good in vivo tumor targetability and the fluorescence of indocyanine green (ICG)-loaded micelles was 4- to 6.6-fold stronger than free ICG within 6 h in HCCLM3 tumor-bearing nude mice. Conclusion: HA-ss-FA is a promising nanocarrier with excellent biocompatibility, tumor targetability, and controlled drug release capability for delivery of chemotherapy drugs in cancer therapy. Keywords: hyaluronic acid, CD44 receptor targeting, redox responsive, folic acid, micelles, doxorubicin
format	article
author	Yang YS Zhao Y Lan JS Kang YN Zhang T Ding Y Zhang XY Lu L
author_facet	Yang YS Zhao Y Lan JS Kang YN Zhang T Ding Y Zhang XY Lu L
author_sort	Yang YS
title	Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery
title_short	Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery
title_full	Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery
title_fullStr	Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery
title_full_unstemmed	Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery
title_sort	reduction-sensitive cd44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery
publisher	Dove Medical Press
publishDate	2018
url	https://doaj.org/article/77724f237d134617b9b9e6cae688df19
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Reduction-sensitive CD44 receptor-targeted hyaluronic acid derivative micelles for doxorubicin delivery

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