Aptamer-functionalized peptide H3CR5C as a novel nanovehicle for codelivery of fasudil and miRNA-195 targeting hepatocellular carcinoma

Ying Liu,1,* Xin Wu,1,* Yuan Gao,2,* Jigang Zhang,1 Dandan Zhang,1 Shengying Gu,1 Guanhua Zhu,1 Gaolin Liu,1 Xiaoyu Li1 1Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 2Department of Pharmaceutics, Changhai Hospital, Second Military Medic...

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Autores principales:	Liu Y, Wu X, Gao Y, Zhang JG, Zhang DD, Gu SY, Zhu GH, Liu GL, Li XY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	aptamer fasudil miR195 combined therapy hepatocellular carcinoma Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e747f13235044edeb83ab312495a531b
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spelling	oai:doaj.org-article:e747f13235044edeb83ab312495a531b2021-12-02T03:58:36ZAptamer-functionalized peptide H3CR5C as a novel nanovehicle for codelivery of fasudil and miRNA-195 targeting hepatocellular carcinoma1178-2013https://doaj.org/article/e747f13235044edeb83ab312495a531b2016-08-01T00:00:00Zhttps://www.dovepress.com/aptamer-functionalized-peptide-h3cr5c-as-a-novel-nanovehicle-for-codel-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Ying Liu,1,* Xin Wu,1,* Yuan Gao,2,* Jigang Zhang,1 Dandan Zhang,1 Shengying Gu,1 Guanhua Zhu,1 Gaolin Liu,1 Xiaoyu Li1 1Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 2Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Liver cancer is the fifth most commonly diagnosed malignancy, of which hepatocellular carcinoma (HCC) represents the dominating histological subtype. Antiangiogenic therapy aimed at vascular endothelial growth factor (VEGF) has shown promising but deficient clinical prospects on account of vasculogenic mimicry, a highly patterned vascular channel distinguished from the endothelium-dependent blood vessel, which may function as blood supply networks occurring in aggressive tumors including HCC. In this study, we used a new cationic peptide, disulfide cross-linked stearylated polyarginine peptide modified with histidine (H3R5), as a reducible vector, cell penetrating peptide-modified aptamer (ST21) with specific binding to HCC cells to conjugate to peptide H3R5 as the targeting probe, miRNA-195 (miR195)as a powerful gene drug to inhibit VEGF, and fasudil to suppress vasculogenic mimicry by blocking ROCK2, all of which were simultaneously encapsulated in the same nanoparticles. Fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient and miR195 was condensed through electrostatic interaction. ST21-H3R5-polyethylene glycol (PEG) exhibited excellent loading capacities for both fasudil and miR195 with adjustable dosing ratios. Western blot analysis showed that FasudilST21-H3R5-PEGmiR195 had strong silencing activity of ROCK2 and VEGF, as compared with FasudilH3R5-PEGmiR195. In vitro and in vivo experiments confirmed that ST21-modified nanoparticles showed significantly higher cellular uptake and therapeutic efficacy in tumor cells or tumor tissues than the unmodified counterparts. These findings suggest that aptamer-conjugated peptide holds great promise for delivering chemical drugs and gene drugs simultaneously to overcome HCC. Keywords: aptamer, fasudil, miR195, combined therapy, hepatocellular carcinomaLiu YWu XGao YZhang JGZhang DDGu SYZhu GHLiu GLLi XYDove Medical PressarticleaptamerfasudilmiR195combined therapyhepatocellular carcinomaMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 3891-3905 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	aptamer fasudil miR195 combined therapy hepatocellular carcinoma Medicine (General) R5-920
spellingShingle	aptamer fasudil miR195 combined therapy hepatocellular carcinoma Medicine (General) R5-920 Liu Y Wu X Gao Y Zhang JG Zhang DD Gu SY Zhu GH Liu GL Li XY Aptamer-functionalized peptide H3CR5C as a novel nanovehicle for codelivery of fasudil and miRNA-195 targeting hepatocellular carcinoma
description	Ying Liu,1,* Xin Wu,1,* Yuan Gao,2,* Jigang Zhang,1 Dandan Zhang,1 Shengying Gu,1 Guanhua Zhu,1 Gaolin Liu,1 Xiaoyu Li1 1Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, 2Department of Pharmaceutics, Changhai Hospital, Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Liver cancer is the fifth most commonly diagnosed malignancy, of which hepatocellular carcinoma (HCC) represents the dominating histological subtype. Antiangiogenic therapy aimed at vascular endothelial growth factor (VEGF) has shown promising but deficient clinical prospects on account of vasculogenic mimicry, a highly patterned vascular channel distinguished from the endothelium-dependent blood vessel, which may function as blood supply networks occurring in aggressive tumors including HCC. In this study, we used a new cationic peptide, disulfide cross-linked stearylated polyarginine peptide modified with histidine (H3R5), as a reducible vector, cell penetrating peptide-modified aptamer (ST21) with specific binding to HCC cells to conjugate to peptide H3R5 as the targeting probe, miRNA-195 (miR195)as a powerful gene drug to inhibit VEGF, and fasudil to suppress vasculogenic mimicry by blocking ROCK2, all of which were simultaneously encapsulated in the same nanoparticles. Fasudil was loaded by ammonium sulfate-induced transmembrane electrochemical gradient and miR195 was condensed through electrostatic interaction. ST21-H3R5-polyethylene glycol (PEG) exhibited excellent loading capacities for both fasudil and miR195 with adjustable dosing ratios. Western blot analysis showed that FasudilST21-H3R5-PEGmiR195 had strong silencing activity of ROCK2 and VEGF, as compared with FasudilH3R5-PEGmiR195. In vitro and in vivo experiments confirmed that ST21-modified nanoparticles showed significantly higher cellular uptake and therapeutic efficacy in tumor cells or tumor tissues than the unmodified counterparts. These findings suggest that aptamer-conjugated peptide holds great promise for delivering chemical drugs and gene drugs simultaneously to overcome HCC. Keywords: aptamer, fasudil, miR195, combined therapy, hepatocellular carcinoma
format	article
author	Liu Y Wu X Gao Y Zhang JG Zhang DD Gu SY Zhu GH Liu GL Li XY
author_facet	Liu Y Wu X Gao Y Zhang JG Zhang DD Gu SY Zhu GH Liu GL Li XY
author_sort	Liu Y
title	Aptamer-functionalized peptide H3CR5C as a novel nanovehicle for codelivery of fasudil and miRNA-195 targeting hepatocellular carcinoma
title_short	Aptamer-functionalized peptide H3CR5C as a novel nanovehicle for codelivery of fasudil and miRNA-195 targeting hepatocellular carcinoma
title_full	Aptamer-functionalized peptide H3CR5C as a novel nanovehicle for codelivery of fasudil and miRNA-195 targeting hepatocellular carcinoma
title_fullStr	Aptamer-functionalized peptide H3CR5C as a novel nanovehicle for codelivery of fasudil and miRNA-195 targeting hepatocellular carcinoma
title_full_unstemmed	Aptamer-functionalized peptide H3CR5C as a novel nanovehicle for codelivery of fasudil and miRNA-195 targeting hepatocellular carcinoma
title_sort	aptamer-functionalized peptide h3cr5c as a novel nanovehicle for codelivery of fasudil and mirna-195 targeting hepatocellular carcinoma
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/e747f13235044edeb83ab312495a531b
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Aptamer-functionalized peptide H3CR5C as a novel nanovehicle for codelivery of fasudil and miRNA-195 targeting hepatocellular carcinoma

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