Modifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form Nano-Medicine

Xiaoyi Zhang, 1, 2 Yixin Zhang, 1, 2 Yaonan Wang, 1, 2 Jianhui Wu, 1, 2 Haiyan Chen, 1, 2 Ming Zhao, 1–3 Shiqi Peng 1, 2 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, B...

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Autores principales:	Zhang X, Zhang Y, Wang Y, Wu J, Chen H, Zhao M, Peng S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	icca modification trp-phe-phe anti-tumor thrombus targeting release toxicity nano-species Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/0b71e198e060471ab3a6f1dd26df725b
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spelling	oai:doaj.org-article:0b71e198e060471ab3a6f1dd26df725b2021-12-02T08:18:59ZModifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form Nano-Medicine1178-2013https://doaj.org/article/0b71e198e060471ab3a6f1dd26df725b2020-01-01T00:00:00Zhttps://www.dovepress.com/modifying-icca-with-trp-phe-phe-to-enhance-in-vivo-activity-and-form-n-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiaoyi Zhang, 1, 2 Yixin Zhang, 1, 2 Yaonan Wang, 1, 2 Jianhui Wu, 1, 2 Haiyan Chen, 1, 2 Ming Zhao, 1–3 Shiqi Peng 1, 2 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, People’s Republic of China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, People’s Republic of China; 3Beijing Laboratory of Biomedical Materials and Key Laboratory of Biomedical Materials of Natural Macromolecules, Department of Biomaterials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100026, People’s Republic of ChinaCorrespondence: Shiqi Peng; Ming ZhaoDepartment of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, No. 10, Youanmenwaixitoutiao, Fengtai District, Beijing 100069, People’s Republic of ChinaTel +86 10 8391 1528; +86 10 8391 1535Fax +86 10 8391 1528; +86 10 8391 1533Email sqpeng@bjmu.edu.cn; maozhao@126.comBackground: 1-(4-isopropylphenyl)-β-carboline-3-carboxylic acid (ICCA) was modified by Trp-Phe-Phe to form 1-(4-isopropylphenyl)-β-carboline-3-carbonyl-Trp-Phe-Phe (ICCA-WFF).Purpose: The object of preparing ICCA-WFF was to enhance the in vivo efficacy of ICCA, to explore the possible targeting action, and to visualize the nano-feature.Methods: The advantages of ICCA-WFF over ICCA were demonstrated by a series of in vivo assays, such as anti-tumor assay, anti-arterial thrombosis assay, anti-venous thrombosis assay, P-selectin expression assay, and GPIIb/IIIa expression assay. The nano-features of ICCA-WFF were visualized by TEM, SEM and AFM images. The thrombus targeting and tumor-targeting actions were evidenced by FT-MS spectrum analysis.Results: The minimal effective dose of ICCA-WFF slowing tumor growth and inhibiting thrombosis was 10-fold lower than that of ICCA. ICCA-WFF, but not ICCA, formed nano-particles capable of safe delivery in blood circulation. In vivo ICCA-WFF, but not ICCA, can target thrombus and tumor. In thrombus and tumor, ICCA-WFF released Trp-Phe-Phe and/or ICCA.Conclusion: Modifying ICCA with Trp-Phe-Phe successfully enhanced the anti-tumor activity, improved the anti-thrombotic action, formed nano-particles, targeted tumor tissue and thrombus, and provided an oligopeptide modification strategy for heterocyclic compounds.Keywords: ICCA, modification, Trp-Phe-Phe, anti-tumor, thrombus targeting, release, toxicity, nano-speciesZhang XZhang YWang YWu JChen HZhao MPeng SDove Medical Pressarticleiccamodificationtrp-phe-pheanti-tumorthrombus targetingreleasetoxicitynano-speciesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 465-481 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	icca modification trp-phe-phe anti-tumor thrombus targeting release toxicity nano-species Medicine (General) R5-920
spellingShingle	icca modification trp-phe-phe anti-tumor thrombus targeting release toxicity nano-species Medicine (General) R5-920 Zhang X Zhang Y Wang Y Wu J Chen H Zhao M Peng S Modifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form Nano-Medicine
description	Xiaoyi Zhang, 1, 2 Yixin Zhang, 1, 2 Yaonan Wang, 1, 2 Jianhui Wu, 1, 2 Haiyan Chen, 1, 2 Ming Zhao, 1–3 Shiqi Peng 1, 2 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, People’s Republic of China; 2Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, People’s Republic of China; 3Beijing Laboratory of Biomedical Materials and Key Laboratory of Biomedical Materials of Natural Macromolecules, Department of Biomaterials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100026, People’s Republic of ChinaCorrespondence: Shiqi Peng; Ming ZhaoDepartment of Medicinal Chemistry, School of Pharmaceutical Sciences, Capital Medical University, No. 10, Youanmenwaixitoutiao, Fengtai District, Beijing 100069, People’s Republic of ChinaTel +86 10 8391 1528; +86 10 8391 1535Fax +86 10 8391 1528; +86 10 8391 1533Email sqpeng@bjmu.edu.cn; maozhao@126.comBackground: 1-(4-isopropylphenyl)-β-carboline-3-carboxylic acid (ICCA) was modified by Trp-Phe-Phe to form 1-(4-isopropylphenyl)-β-carboline-3-carbonyl-Trp-Phe-Phe (ICCA-WFF).Purpose: The object of preparing ICCA-WFF was to enhance the in vivo efficacy of ICCA, to explore the possible targeting action, and to visualize the nano-feature.Methods: The advantages of ICCA-WFF over ICCA were demonstrated by a series of in vivo assays, such as anti-tumor assay, anti-arterial thrombosis assay, anti-venous thrombosis assay, P-selectin expression assay, and GPIIb/IIIa expression assay. The nano-features of ICCA-WFF were visualized by TEM, SEM and AFM images. The thrombus targeting and tumor-targeting actions were evidenced by FT-MS spectrum analysis.Results: The minimal effective dose of ICCA-WFF slowing tumor growth and inhibiting thrombosis was 10-fold lower than that of ICCA. ICCA-WFF, but not ICCA, formed nano-particles capable of safe delivery in blood circulation. In vivo ICCA-WFF, but not ICCA, can target thrombus and tumor. In thrombus and tumor, ICCA-WFF released Trp-Phe-Phe and/or ICCA.Conclusion: Modifying ICCA with Trp-Phe-Phe successfully enhanced the anti-tumor activity, improved the anti-thrombotic action, formed nano-particles, targeted tumor tissue and thrombus, and provided an oligopeptide modification strategy for heterocyclic compounds.Keywords: ICCA, modification, Trp-Phe-Phe, anti-tumor, thrombus targeting, release, toxicity, nano-species
format	article
author	Zhang X Zhang Y Wang Y Wu J Chen H Zhao M Peng S
author_facet	Zhang X Zhang Y Wang Y Wu J Chen H Zhao M Peng S
author_sort	Zhang X
title	Modifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form Nano-Medicine
title_short	Modifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form Nano-Medicine
title_full	Modifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form Nano-Medicine
title_fullStr	Modifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form Nano-Medicine
title_full_unstemmed	Modifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form Nano-Medicine
title_sort	modifying icca with trp-phe-phe to enhance in vivo activity and form nano-medicine
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/0b71e198e060471ab3a6f1dd26df725b
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Modifying ICCA with Trp-Phe-Phe to Enhance in vivo Activity and Form Nano-Medicine

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