Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach

Shaofeng Lou,1 Xiuyuan Zhang,2 Mingming Zhang,2 Shenglu Ji,1 Weiwei Wang,2 Ju Zhang,1 Chen Li,2 Deling Kong1,2 1Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, 2Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Enginee...

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Autores principales:	Lou S, Zhang X, Zhang M, Ji S, Wang W, Zhang J, Li C, Kong D
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Glycopolymer Multi responsive nanogel Hepatoma targeting Drug delivery Arm First ATRP Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c49e637b90a34c629ebde56dc2b91acb
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spelling	oai:doaj.org-article:c49e637b90a34c629ebde56dc2b91acb2021-12-02T05:14:20ZPreparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach1178-2013https://doaj.org/article/c49e637b90a34c629ebde56dc2b91acb2017-05-01T00:00:00Zhttps://www.dovepress.com/preparation-of-a-dual-cored-hepatoma-specific-star-glycopolymer-nanoge-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Shaofeng Lou,1 Xiuyuan Zhang,2 Mingming Zhang,2 Shenglu Ji,1 Weiwei Wang,2 Ju Zhang,1 Chen Li,2 Deling Kong1,2 1Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, 2Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin, People’s Republic of China Abstract: A reductase-cleavable and thermo-responsive star-shaped polymer nanogel was prepared via an “arm-first” atom transfer radical polymerization approach. The nanogel consists of a thermo- and redox-sensitive core and a zwitterionic copolymer block. The dual sensitive core is composed of poly(N-isopropylacrylamide) that is formed by disulfide crosslinking of N-isopropylacrylamide. The zwitterionic copolymer block contains a poly(sulfobetaine methacrylate) component, a known anti-adsorptive moiety that extends blood circulation time, and a lactose motif of poly(2-lactobionamidoethyl methacrylamide) that specifically targets the asialoglycoprotein receptors (ASGP-Rs) of hepatoma. Doxorubicin (DOX) was encapsulated into the cross-linked nanogels via solvent extraction/evaporation method and dialysis; average diameter of both blank and DOX-loaded nanogels was ~120 nm. The multi-responsiveness of nanogel drug release in different temperatures and redox conditions was assessed. After 24 h, DOX release was only ~20% at 30°C with 0 mM glutathione (GSH), whereas over 90% DOX release was observed at 40°C and 10 mM GSH, evidence of dual responsiveness to temperature and reductase GSH. The IC50 value of DOX-loaded nanogels was much lower in human hepatoma (HepG2) cells compared to non-hepatic HeLa cells. Remarkably, DOX uptake of HepG2 cells differed substantially in the presence and absence of galactose (0.31 vs 1.42 µg/mL after 48 h of incubation). The difference was non-detectable in HeLa cells (1.21 vs 1.57 µg/mL after 48 h of incubation), indicating that the overexpression of ASGP-Rs leads to the DOX-loaded lactosylated nanogels actively targeting hepatoma. Our data indicate that the lactose-decorated star-shaped nanogels are dual responsive and hepatoma targeted, and could be employed as hepatoma-specific anti-cancer drug delivery vehicle for cancer chemotherapy. Keywords: glycopolymer, multi-responsive nanogel, hepatoma targeting, drug delivery, arm-first ATRPLou SZhang XZhang MJi SWang WZhang JLi CKong DDove Medical PressarticleGlycopolymerMulti responsive nanogelHepatoma targetingDrug deliveryArm First ATRPMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 3653-3664 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Glycopolymer Multi responsive nanogel Hepatoma targeting Drug delivery Arm First ATRP Medicine (General) R5-920
spellingShingle	Glycopolymer Multi responsive nanogel Hepatoma targeting Drug delivery Arm First ATRP Medicine (General) R5-920 Lou S Zhang X Zhang M Ji S Wang W Zhang J Li C Kong D Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach
description	Shaofeng Lou,1 Xiuyuan Zhang,2 Mingming Zhang,2 Shenglu Ji,1 Weiwei Wang,2 Ju Zhang,1 Chen Li,2 Deling Kong1,2 1Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, 2Tianjin Key Laboratory of Biomaterial Research, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Tianjin, People’s Republic of China Abstract: A reductase-cleavable and thermo-responsive star-shaped polymer nanogel was prepared via an “arm-first” atom transfer radical polymerization approach. The nanogel consists of a thermo- and redox-sensitive core and a zwitterionic copolymer block. The dual sensitive core is composed of poly(N-isopropylacrylamide) that is formed by disulfide crosslinking of N-isopropylacrylamide. The zwitterionic copolymer block contains a poly(sulfobetaine methacrylate) component, a known anti-adsorptive moiety that extends blood circulation time, and a lactose motif of poly(2-lactobionamidoethyl methacrylamide) that specifically targets the asialoglycoprotein receptors (ASGP-Rs) of hepatoma. Doxorubicin (DOX) was encapsulated into the cross-linked nanogels via solvent extraction/evaporation method and dialysis; average diameter of both blank and DOX-loaded nanogels was ~120 nm. The multi-responsiveness of nanogel drug release in different temperatures and redox conditions was assessed. After 24 h, DOX release was only ~20% at 30°C with 0 mM glutathione (GSH), whereas over 90% DOX release was observed at 40°C and 10 mM GSH, evidence of dual responsiveness to temperature and reductase GSH. The IC50 value of DOX-loaded nanogels was much lower in human hepatoma (HepG2) cells compared to non-hepatic HeLa cells. Remarkably, DOX uptake of HepG2 cells differed substantially in the presence and absence of galactose (0.31 vs 1.42 µg/mL after 48 h of incubation). The difference was non-detectable in HeLa cells (1.21 vs 1.57 µg/mL after 48 h of incubation), indicating that the overexpression of ASGP-Rs leads to the DOX-loaded lactosylated nanogels actively targeting hepatoma. Our data indicate that the lactose-decorated star-shaped nanogels are dual responsive and hepatoma targeted, and could be employed as hepatoma-specific anti-cancer drug delivery vehicle for cancer chemotherapy. Keywords: glycopolymer, multi-responsive nanogel, hepatoma targeting, drug delivery, arm-first ATRP
format	article
author	Lou S Zhang X Zhang M Ji S Wang W Zhang J Li C Kong D
author_facet	Lou S Zhang X Zhang M Ji S Wang W Zhang J Li C Kong D
author_sort	Lou S
title	Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach
title_short	Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach
title_full	Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach
title_fullStr	Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach
title_full_unstemmed	Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach
title_sort	preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first atrp approach
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/c49e637b90a34c629ebde56dc2b91acb
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Preparation of a dual cored hepatoma-specific star glycopolymer nanogel via arm-first ATRP approach

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