ATIQCTPC: a nanomedicine capable of targeting tumor and blocking thrombosis in vivo

Xinyi Xu,1 Yuji Wang,1 Jianhui Wu,1 Xi Hu,1 Haimei Zhu,1 Xiaoyi Zhang,1 Yaonan Wang,1 Lin Gui,1 Ming Zhao,1,2 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory...

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Autores principales:	Xu X, Wang Y, Wu J, Hu X, Zhu H, Zhang X, Wang YN, Gui L, Zhao M, Peng S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Tumor Thrombosis Targeting Nanoparticle TNF-α IL-8 P-Selectin Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3558bb4ce83c454b89c230f0ea3fefeb
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spelling	oai:doaj.org-article:3558bb4ce83c454b89c230f0ea3fefeb2021-12-02T03:11:40ZATIQCTPC: a nanomedicine capable of targeting tumor and blocking thrombosis in vivo1178-2013https://doaj.org/article/3558bb4ce83c454b89c230f0ea3fefeb2017-06-01T00:00:00Zhttps://www.dovepress.com/atiqctpc-a-nanomedicine-capable-of-targeting-tumor-and-blocking-thromb-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xinyi Xu,1 Yuji Wang,1 Jianhui Wu,1 Xi Hu,1 Haimei Zhu,1 Xiaoyi Zhang,1 Yaonan Wang,1 Lin Gui,1 Ming Zhao,1,2 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China Abstract: To overcome the harmful side effects, low tolerance, and undesirable outcomes of the anticancer drugs, we used ethane-1,2-diamine to bridge antitumoral (S)-3-acetyl-4-oxo-tetrahydroindolo[2,3-a]quinolizine-6-carboxylic acid (ATIQC) and tumor-targeting d-glucuronic acid, thereby providing (6S)-3-acetyl-4-oxo-N-(2-(3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxamido)ethyl)-4,6,7,12-tetrahydroindolo[2,3-a]quinolizine-6-carboxamide (ATIQCTPC). Atomic force microscopy images visualized, that in serum, ATIQCTPC formed particles of height <81 nm. These particles effectively avoided phagocytosis of macrophages and were stable in blood circulation. Distribution analysis indicated that ATIQCTPC accumulated and released ATIQC in the tumor tissue through a targeting manner. Thus, the antitumor and the anti-thrombotic activities of ATIQCTPC were 100-fold higher than those of ATIQC, and ATIQCTPC was able to prevent cancer patients from suffering from thrombosis. Based on the observation that ATIQCTPC decreased serum tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in S180 mice, we hypothesized that this is the mechanism that ATIQCTPC utilized to slow tumor growth. Additionally, we observed that ATIQCTPC inhibited thrombosis by decreasing serum P-selectin of thrombotic rats. The intermolecular association and the hexamerization manner of ATIQCTPC were experimentally evidenced and correlated with the formation of the nanoparticles. Keywords: tumor, thrombosis, targeting, nanoparticle, TNF-α, IL-8, P-selectinXu XWang YWu JHu XZhu HZhang XWang YNGui LZhao MPeng SDove Medical PressarticleTumorThrombosisTargetingNanoparticleTNF-αIL-8P-SelectinMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 4415-4431 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Tumor Thrombosis Targeting Nanoparticle TNF-α IL-8 P-Selectin Medicine (General) R5-920
spellingShingle	Tumor Thrombosis Targeting Nanoparticle TNF-α IL-8 P-Selectin Medicine (General) R5-920 Xu X Wang Y Wu J Hu X Zhu H Zhang X Wang YN Gui L Zhao M Peng S ATIQCTPC: a nanomedicine capable of targeting tumor and blocking thrombosis in vivo
description	Xinyi Xu,1 Yuji Wang,1 Jianhui Wu,1 Xi Hu,1 Haimei Zhu,1 Xiaoyi Zhang,1 Yaonan Wang,1 Lin Gui,1 Ming Zhao,1,2 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China Abstract: To overcome the harmful side effects, low tolerance, and undesirable outcomes of the anticancer drugs, we used ethane-1,2-diamine to bridge antitumoral (S)-3-acetyl-4-oxo-tetrahydroindolo[2,3-a]quinolizine-6-carboxylic acid (ATIQC) and tumor-targeting d-glucuronic acid, thereby providing (6S)-3-acetyl-4-oxo-N-(2-(3,4,5,6-tetrahydroxytetrahydro-2H-pyran-2-carboxamido)ethyl)-4,6,7,12-tetrahydroindolo[2,3-a]quinolizine-6-carboxamide (ATIQCTPC). Atomic force microscopy images visualized, that in serum, ATIQCTPC formed particles of height <81 nm. These particles effectively avoided phagocytosis of macrophages and were stable in blood circulation. Distribution analysis indicated that ATIQCTPC accumulated and released ATIQC in the tumor tissue through a targeting manner. Thus, the antitumor and the anti-thrombotic activities of ATIQCTPC were 100-fold higher than those of ATIQC, and ATIQCTPC was able to prevent cancer patients from suffering from thrombosis. Based on the observation that ATIQCTPC decreased serum tumor necrosis factor-α (TNF-α) and interleukin-8 (IL-8) in S180 mice, we hypothesized that this is the mechanism that ATIQCTPC utilized to slow tumor growth. Additionally, we observed that ATIQCTPC inhibited thrombosis by decreasing serum P-selectin of thrombotic rats. The intermolecular association and the hexamerization manner of ATIQCTPC were experimentally evidenced and correlated with the formation of the nanoparticles. Keywords: tumor, thrombosis, targeting, nanoparticle, TNF-α, IL-8, P-selectin
format	article
author	Xu X Wang Y Wu J Hu X Zhu H Zhang X Wang YN Gui L Zhao M Peng S
author_facet	Xu X Wang Y Wu J Hu X Zhu H Zhang X Wang YN Gui L Zhao M Peng S
author_sort	Xu X
title	ATIQCTPC: a nanomedicine capable of targeting tumor and blocking thrombosis in vivo
title_short	ATIQCTPC: a nanomedicine capable of targeting tumor and blocking thrombosis in vivo
title_full	ATIQCTPC: a nanomedicine capable of targeting tumor and blocking thrombosis in vivo
title_fullStr	ATIQCTPC: a nanomedicine capable of targeting tumor and blocking thrombosis in vivo
title_full_unstemmed	ATIQCTPC: a nanomedicine capable of targeting tumor and blocking thrombosis in vivo
title_sort	atiqctpc: a nanomedicine capable of targeting tumor and blocking thrombosis in vivo
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/3558bb4ce83c454b89c230f0ea3fefeb
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_version_	1718401845647376384

ATIQCTPC: a nanomedicine capable of targeting tumor and blocking thrombosis in vivo

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