TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting

Feng-Ying Chen,1 Jing-Jing Yan,1 Han-Xi Yi,2 Fu-Qiang Hu,2 Yong-Zhong Du,2 Hong Yuan,2 Jian You,2 Meng-Dan Zhao1 1Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2College of Pharmaceutical Science, Zhejiang University, Hangzhou,...

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Autores principales:	Chen FY, Yan JJ, Yi HX, Hu FQ, Du YZ, Yuan H, You J, Zhao MD
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/03183d1f0208473aab6b119a72579b28
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spelling	oai:doaj.org-article:03183d1f0208473aab6b119a72579b282021-12-02T03:05:08ZTNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting1178-2013https://doaj.org/article/03183d1f0208473aab6b119a72579b282014-09-01T00:00:00Zhttp://www.dovepress.com/tnyl-peptide-functional-chitosan-g-stearate-conjugate-micelles-for-tum-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Feng-Ying Chen,1 Jing-Jing Yan,1 Han-Xi Yi,2 Fu-Qiang Hu,2 Yong-Zhong Du,2 Hong Yuan,2 Jian You,2 Meng-Dan Zhao1 1Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2College of Pharmaceutical Science, Zhejiang University, Hangzhou, People’s Republic of China Abstract: Nowadays, a real challenge in cancer therapy is to design drug delivery systems that can achieve high concentrations of drugs at the target site for improved therapeutic effect with reduced side effects. In this research, we designed and synthesized a homing peptide-(TNYLFSPNGPIA, TNYL) modified chitosan-g-stearate (CS) polymer micelle (named T-CS) for targeting delivery. The peptide displayed specific binding affinity to EphB4 which is a member of the Eph family of receptor tyrosine protein kinases. The amphiphilic polymer T-CS can gather into micelles by themselves in an aqueous environment with a low critical micelle concentration value (91.2 µg/L) and nano-scaled size (82.1±2.8 nm). The drug encapsulation efficiency reached 86.43% after loading the hydrophobic drug doxorubicin (DOX). The cytotoxicity of T-CS/DOX against SKOV3 cells was enhanced by approximately 2.3-fold when compared with CS/DOX. The quantitative and qualitative analysis for cellular uptake indicated that TNYL modification can markedly increase cellular internalization in the EphB4-overexpressing SKOV3 cell line, especially with a short incubation time. It is interesting that relatively higher uptake of the T-CS/DOX micelles by SKOV3 cells (positive-EphB4) than A549 cells (negative-EphB4) was observed when the two cells were co-incubated. Furthermore, in vivo distribution experiment using a bilateral-tumor model showed that there was more fluorescence accumulation in the SKOV3 tumor than in the A549 tumor over the whole experiment. These results suggest that TNYL-modified CS micelles may be promising drug carriers as targeting therapy for the EphB4-overexpressing tumor. Keywords: chitosan-g-stearate, polymeric micelles, TNYL, active targeting, antitumor activityChen FYYan JJYi HXHu FQDu YZYuan HYou JZhao MDDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 4597-4608 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Chen FY Yan JJ Yi HX Hu FQ Du YZ Yuan H You J Zhao MD TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting
description	Feng-Ying Chen,1 Jing-Jing Yan,1 Han-Xi Yi,2 Fu-Qiang Hu,2 Yong-Zhong Du,2 Hong Yuan,2 Jian You,2 Meng-Dan Zhao1 1Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2College of Pharmaceutical Science, Zhejiang University, Hangzhou, People’s Republic of China Abstract: Nowadays, a real challenge in cancer therapy is to design drug delivery systems that can achieve high concentrations of drugs at the target site for improved therapeutic effect with reduced side effects. In this research, we designed and synthesized a homing peptide-(TNYLFSPNGPIA, TNYL) modified chitosan-g-stearate (CS) polymer micelle (named T-CS) for targeting delivery. The peptide displayed specific binding affinity to EphB4 which is a member of the Eph family of receptor tyrosine protein kinases. The amphiphilic polymer T-CS can gather into micelles by themselves in an aqueous environment with a low critical micelle concentration value (91.2 µg/L) and nano-scaled size (82.1±2.8 nm). The drug encapsulation efficiency reached 86.43% after loading the hydrophobic drug doxorubicin (DOX). The cytotoxicity of T-CS/DOX against SKOV3 cells was enhanced by approximately 2.3-fold when compared with CS/DOX. The quantitative and qualitative analysis for cellular uptake indicated that TNYL modification can markedly increase cellular internalization in the EphB4-overexpressing SKOV3 cell line, especially with a short incubation time. It is interesting that relatively higher uptake of the T-CS/DOX micelles by SKOV3 cells (positive-EphB4) than A549 cells (negative-EphB4) was observed when the two cells were co-incubated. Furthermore, in vivo distribution experiment using a bilateral-tumor model showed that there was more fluorescence accumulation in the SKOV3 tumor than in the A549 tumor over the whole experiment. These results suggest that TNYL-modified CS micelles may be promising drug carriers as targeting therapy for the EphB4-overexpressing tumor. Keywords: chitosan-g-stearate, polymeric micelles, TNYL, active targeting, antitumor activity
format	article
author	Chen FY Yan JJ Yi HX Hu FQ Du YZ Yuan H You J Zhao MD
author_facet	Chen FY Yan JJ Yi HX Hu FQ Du YZ Yuan H You J Zhao MD
author_sort	Chen FY
title	TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting
title_short	TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting
title_full	TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting
title_fullStr	TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting
title_full_unstemmed	TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting
title_sort	tnyl peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/03183d1f0208473aab6b119a72579b28
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TNYL peptide functional chitosan-g-stearate conjugate micelles for tumor specific targeting

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