Decoration of pH-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin

Qing Chen,1,* Miaomiao Long,2,* Lipeng Qiu,3 Mengqin Zhu,3 Zhen Li,1 Mingxi Qiao,1 Haiyang Hu,1 Xiuli Zhao,1 Dawei Chen1 1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 2Department of Research and Development, Nanjing Chia Tai Tianqing Pharmaceutical...

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Autores principales:	Chen Q, Long MM, Qiu LP, Zhu MQ, Li Z, Qiao MX, Hu HY, Zhao XL, Chen DW
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Her2 peptide pH-sensitive micelles hyaluronic acid antitumor efficacy doxorubicin Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d8da20e5623c432bb206b21468631c72
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spelling	oai:doaj.org-article:d8da20e5623c432bb206b21468631c722021-12-02T06:16:23ZDecoration of pH-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin1178-2013https://doaj.org/article/d8da20e5623c432bb206b21468631c722016-10-01T00:00:00Zhttps://www.dovepress.com/decoration-of-ph-sensitive-copolymer-micelles-with-tumor-specific-pept-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Qing Chen,1,* Miaomiao Long,2,* Lipeng Qiu,3 Mengqin Zhu,3 Zhen Li,1 Mingxi Qiao,1 Haiyang Hu,1 Xiuli Zhao,1 Dawei Chen1 1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 2Department of Research and Development, Nanjing Chia Tai Tianqing Pharmaceutical Group Co. Ltd, Nanjing, 3Department of Pharmaceutics, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, People’s Republic of China *These authors contributed equally to this work Abstract: To improve the targeting efficacy of hyaluronic acid (HA)-based micelles, pH-sensitive mixed micelles based on HA-g-poly(L-histidine) (PHis) and d-α-tocopheryl polyethylene glycol 2000 copolymers were prepared and decorated with human epidermal growth factor receptor 2 (Her2) peptide, a tumor cell-specific peptide ligand, on their surface. The doxorubicin-loaded micelles (HA-PHis/peptide–d-α-tocopheryl polyethylene glycol 2000 mixed micelles [PHTM]) were characterized to have a unimodal size distribution and pH-dependent drug release pattern. In vitro tumor targeting studies demonstrated that PHTM exhibited the pronounced cytotoxicity and efficient internalization in MDA-MB-231 cells overexpressing CD44 and Her2 receptors. In vivo investigation into micelles in MDA-MB-231 tumor-bearing mice confirmed that PTHM could reach the tumor site more effectively and exert excellent tumor killing activity. In general, Her2 peptide decoration can enhance the selective cytotoxicity and antitumor activity of HA-based micelles. Keywords: Her2 peptide, hyaluronic acid, poly(L-histidine), targeted delivery, antitumor efficacyChen QLong MMQiu LPZhu MQLi ZQiao MXHu HYZhao XLChen DWDove Medical PressarticleHer2 peptidepH-sensitive micelleshyaluronic acidantitumor efficacydoxorubicinMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 5415-5427 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Her2 peptide pH-sensitive micelles hyaluronic acid antitumor efficacy doxorubicin Medicine (General) R5-920
spellingShingle	Her2 peptide pH-sensitive micelles hyaluronic acid antitumor efficacy doxorubicin Medicine (General) R5-920 Chen Q Long MM Qiu LP Zhu MQ Li Z Qiao MX Hu HY Zhao XL Chen DW Decoration of pH-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin
description	Qing Chen,1,* Miaomiao Long,2,* Lipeng Qiu,3 Mengqin Zhu,3 Zhen Li,1 Mingxi Qiao,1 Haiyang Hu,1 Xiuli Zhao,1 Dawei Chen1 1Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 2Department of Research and Development, Nanjing Chia Tai Tianqing Pharmaceutical Group Co. Ltd, Nanjing, 3Department of Pharmaceutics, School of Pharmaceutical Sciences, Jiangnan University, Wuxi, People’s Republic of China *These authors contributed equally to this work Abstract: To improve the targeting efficacy of hyaluronic acid (HA)-based micelles, pH-sensitive mixed micelles based on HA-g-poly(L-histidine) (PHis) and d-α-tocopheryl polyethylene glycol 2000 copolymers were prepared and decorated with human epidermal growth factor receptor 2 (Her2) peptide, a tumor cell-specific peptide ligand, on their surface. The doxorubicin-loaded micelles (HA-PHis/peptide–d-α-tocopheryl polyethylene glycol 2000 mixed micelles [PHTM]) were characterized to have a unimodal size distribution and pH-dependent drug release pattern. In vitro tumor targeting studies demonstrated that PHTM exhibited the pronounced cytotoxicity and efficient internalization in MDA-MB-231 cells overexpressing CD44 and Her2 receptors. In vivo investigation into micelles in MDA-MB-231 tumor-bearing mice confirmed that PTHM could reach the tumor site more effectively and exert excellent tumor killing activity. In general, Her2 peptide decoration can enhance the selective cytotoxicity and antitumor activity of HA-based micelles. Keywords: Her2 peptide, hyaluronic acid, poly(L-histidine), targeted delivery, antitumor efficacy
format	article
author	Chen Q Long MM Qiu LP Zhu MQ Li Z Qiao MX Hu HY Zhao XL Chen DW
author_facet	Chen Q Long MM Qiu LP Zhu MQ Li Z Qiao MX Hu HY Zhao XL Chen DW
author_sort	Chen Q
title	Decoration of pH-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin
title_short	Decoration of pH-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin
title_full	Decoration of pH-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin
title_fullStr	Decoration of pH-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin
title_full_unstemmed	Decoration of pH-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin
title_sort	decoration of ph-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/d8da20e5623c432bb206b21468631c72
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Decoration of pH-sensitive copolymer micelles with tumor-specific peptide for enhanced cellular uptake of doxorubicin

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