siRNA-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cell-penetrating and endosomal escape capacities for suppressing breast tumor metastasis

Ping Sun,1 Wei Huang,1 Lin Kang,1 Mingji Jin,1 Bo Fan,1 Hongyan Jin,2 Qi-Ming Wang,1 Zhonggao Gao1 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical C...

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Autores principales:	Sun P, Huang W, Kang L, Jin M, Fan B, Jin H, Wang Q, Gao Z
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Poly(histidine-arginine)6 peptide modified chitosan nanoparticle Cell penetrating peptides Endosome/lysosome escape Gene delivery Breast carcinoma Abbreviations Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/7b95d9a0a1414f7d9cd67ea76cd89462
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spelling	oai:doaj.org-article:7b95d9a0a1414f7d9cd67ea76cd894622021-12-02T03:58:38ZsiRNA-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cell-penetrating and endosomal escape capacities for suppressing breast tumor metastasis1178-2013https://doaj.org/article/7b95d9a0a1414f7d9cd67ea76cd894622017-04-01T00:00:00Zhttps://www.dovepress.com/sirna-loaded-polyhistidine-arginine6-modified-chitosan-nanoparticle-wi-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ping Sun,1 Wei Huang,1 Lin Kang,1 Mingji Jin,1 Bo Fan,1 Hongyan Jin,2 Qi-Ming Wang,1 Zhonggao Gao1 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2Yanbian University Hospital, Jilin, People’s Republic of China Abstract: An ideal carrier that delivers small interfering RNA (siRNA) should be designed based on two criteria: cellular-mediated internalization and endosomal escape. Poly(histidine-arginine)6(H6R6) peptide was introduced into chitosan (CS) to create a new CS derivative for siRNA delivery, 6-polyarginine (R6) as cell-penetrating peptides facilitated nanoparticle cellular internalization has been proved in our previous research, and 6-polyhistidine (H6) mediated the nanoparticle endosome escape resulted in the siRNA rapid releasing into tumor cytoplasm. H6R6-modified CS nanoparticles showed higher transfection efficiency and better endosomal escape capacity compared to ungroomed CS nanoparticle in vitro. Noticeably, H6R6-modified CS nanoparticles effectively inhibited tumor cell growth and metastases in vivo and significantly improved survival ratio. Therefore, we concluded that H6R6-modified CS copolymer can act as an ideal carrier for siRNA delivery and as a promising candidate in breast cancer therapy. Keywords: poly(histidine-arginine)6-peptide-modified chitosan nanoparticle, cell-penetrating peptides, endosome/lysosome escape, gene delivery, breast carcinomaSun PHuang WKang LJin MFan BJin HWang QGao ZDove Medical PressarticlePoly(histidine-arginine)6 peptide modified chitosan nanoparticleCell penetrating peptidesEndosome/lysosome escapeGene deliveryBreast carcinoma AbbreviationsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 3221-3234 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Poly(histidine-arginine)6 peptide modified chitosan nanoparticle Cell penetrating peptides Endosome/lysosome escape Gene delivery Breast carcinoma Abbreviations Medicine (General) R5-920
spellingShingle	Poly(histidine-arginine)6 peptide modified chitosan nanoparticle Cell penetrating peptides Endosome/lysosome escape Gene delivery Breast carcinoma Abbreviations Medicine (General) R5-920 Sun P Huang W Kang L Jin M Fan B Jin H Wang Q Gao Z siRNA-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cell-penetrating and endosomal escape capacities for suppressing breast tumor metastasis
description	Ping Sun,1 Wei Huang,1 Lin Kang,1 Mingji Jin,1 Bo Fan,1 Hongyan Jin,2 Qi-Ming Wang,1 Zhonggao Gao1 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of Pharmaceutics, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 2Yanbian University Hospital, Jilin, People’s Republic of China Abstract: An ideal carrier that delivers small interfering RNA (siRNA) should be designed based on two criteria: cellular-mediated internalization and endosomal escape. Poly(histidine-arginine)6(H6R6) peptide was introduced into chitosan (CS) to create a new CS derivative for siRNA delivery, 6-polyarginine (R6) as cell-penetrating peptides facilitated nanoparticle cellular internalization has been proved in our previous research, and 6-polyhistidine (H6) mediated the nanoparticle endosome escape resulted in the siRNA rapid releasing into tumor cytoplasm. H6R6-modified CS nanoparticles showed higher transfection efficiency and better endosomal escape capacity compared to ungroomed CS nanoparticle in vitro. Noticeably, H6R6-modified CS nanoparticles effectively inhibited tumor cell growth and metastases in vivo and significantly improved survival ratio. Therefore, we concluded that H6R6-modified CS copolymer can act as an ideal carrier for siRNA delivery and as a promising candidate in breast cancer therapy. Keywords: poly(histidine-arginine)6-peptide-modified chitosan nanoparticle, cell-penetrating peptides, endosome/lysosome escape, gene delivery, breast carcinoma
format	article
author	Sun P Huang W Kang L Jin M Fan B Jin H Wang Q Gao Z
author_facet	Sun P Huang W Kang L Jin M Fan B Jin H Wang Q Gao Z
author_sort	Sun P
title	siRNA-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cell-penetrating and endosomal escape capacities for suppressing breast tumor metastasis
title_short	siRNA-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cell-penetrating and endosomal escape capacities for suppressing breast tumor metastasis
title_full	siRNA-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cell-penetrating and endosomal escape capacities for suppressing breast tumor metastasis
title_fullStr	siRNA-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cell-penetrating and endosomal escape capacities for suppressing breast tumor metastasis
title_full_unstemmed	siRNA-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cell-penetrating and endosomal escape capacities for suppressing breast tumor metastasis
title_sort	sirna-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cell-penetrating and endosomal escape capacities for suppressing breast tumor metastasis
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/7b95d9a0a1414f7d9cd67ea76cd89462
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siRNA-loaded poly(histidine-arginine)6-modified chitosan nanoparticle with enhanced cell-penetrating and endosomal escape capacities for suppressing breast tumor metastasis

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