Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis

Shan Li,1 Yuji Wang,1 Feng Wang,1 Yaonan Wang,1 Xiaoyi Zhang,1 Ming Zhao,1,2 Qiqi Feng,1 Jianhui Wu,1 Shurui Zhao,1 Wei Wu,3 Shiqi Peng11Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing Laboratory of Biomedical Materials, Engineering Research Center of En...

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Autores principales:	Li S, Wang Y, Wang F, Zhang X, Zhao M, Feng Q, Wu J, Zhao S, Wu W, Peng S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/abcc052591544c27a9d529ab6a9538db
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spelling	oai:doaj.org-article:abcc052591544c27a9d529ab6a9538db2021-12-02T00:07:18ZSmall molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis1178-2013https://doaj.org/article/abcc052591544c27a9d529ab6a9538db2015-08-01T00:00:00Zhttp://www.dovepress.com/small-molecule-pzl318-forming-fluorescent-nanoparticles-capable-of-tra-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Shan Li,1 Yuji Wang,1 Feng Wang,1 Yaonan Wang,1 Xiaoyi Zhang,1 Ming Zhao,1,2 Qiqi Feng,1 Jianhui Wu,1 Shurui Zhao,1 Wei Wu,3 Shiqi Peng11Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing Laboratory of Biomedical Materials, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of China; 2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 3College of Basic Medicine of Capital Medical University, Beijing, People’s Republic of ChinaAbstract: Low selectivity of chemotherapy correlates with poor outcomes of cancer patients. To improve this issue, a novel agent, N-(1-[3-methoxycarbonyl-4-hydroxyphenyl]-β-carboline-3-carbonyl)-Trp-Lys-OBzl (PZL318), was reported here. The transmission electron microscopy, scanning electron microscopy, and atomic force microscopy images demonstrated that PZL318 can form nanoparticles. Fluorescent and confocal images visualized that PZL318 formed fluorescent nanoparticles capable of targeting cancer cells and tracing their interactions with cancer cells. In vitro, 40 µM of PZL318 inhibited the proliferation of tumorigenic cells, but not nontumorigenic cells. In vivo, 10 nmol/kg of PZL318 slowed the tumor growth of S180 mice and alleviated the thrombosis of ferric chloride-treated ICR mice, while 100 µmol/kg of PZL318 did not injure healthy mice and they exhibited no liver toxicity. By analyzing Fourier transform–mass spectrometry and rotating-frame Overhauser spectroscopy (ROESY) two-dimensional nuclear magnetic resonance spectra, the chemical mechanism of PZL318-forming trimers and nanoparticles was explored. By using mesoscale simulation, a nanoparticle of 3.01 nm in diameter was predicted containing 13 trimers. Scavenging free radicals, downregulating sP-selectin expression and intercalating toward DNA were correlated with the antitumor mechanism of PZL318.Keywords: nanoparticles, cancer target, sP-selectin, nanomechanism, action mechanism, fluorescent tracerLi SWang YWang FWang YZhang XZhao MFeng QWu JZhao SWu WPeng SDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 5273-5292 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Li S Wang Y Wang F Wang Y Zhang X Zhao M Feng Q Wu J Zhao S Wu W Peng S Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis
description	Shan Li,1 Yuji Wang,1 Feng Wang,1 Yaonan Wang,1 Xiaoyi Zhang,1 Ming Zhao,1,2 Qiqi Feng,1 Jianhui Wu,1 Shurui Zhao,1 Wei Wu,3 Shiqi Peng11Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Beijing Laboratory of Biomedical Materials, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, College of Pharmaceutical Sciences of Capital Medical University, Beijing, People’s Republic of China; 2Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan; 3College of Basic Medicine of Capital Medical University, Beijing, People’s Republic of ChinaAbstract: Low selectivity of chemotherapy correlates with poor outcomes of cancer patients. To improve this issue, a novel agent, N-(1-[3-methoxycarbonyl-4-hydroxyphenyl]-β-carboline-3-carbonyl)-Trp-Lys-OBzl (PZL318), was reported here. The transmission electron microscopy, scanning electron microscopy, and atomic force microscopy images demonstrated that PZL318 can form nanoparticles. Fluorescent and confocal images visualized that PZL318 formed fluorescent nanoparticles capable of targeting cancer cells and tracing their interactions with cancer cells. In vitro, 40 µM of PZL318 inhibited the proliferation of tumorigenic cells, but not nontumorigenic cells. In vivo, 10 nmol/kg of PZL318 slowed the tumor growth of S180 mice and alleviated the thrombosis of ferric chloride-treated ICR mice, while 100 µmol/kg of PZL318 did not injure healthy mice and they exhibited no liver toxicity. By analyzing Fourier transform–mass spectrometry and rotating-frame Overhauser spectroscopy (ROESY) two-dimensional nuclear magnetic resonance spectra, the chemical mechanism of PZL318-forming trimers and nanoparticles was explored. By using mesoscale simulation, a nanoparticle of 3.01 nm in diameter was predicted containing 13 trimers. Scavenging free radicals, downregulating sP-selectin expression and intercalating toward DNA were correlated with the antitumor mechanism of PZL318.Keywords: nanoparticles, cancer target, sP-selectin, nanomechanism, action mechanism, fluorescent tracer
format	article
author	Li S Wang Y Wang F Wang Y Zhang X Zhao M Feng Q Wu J Zhao S Wu W Peng S
author_facet	Li S Wang Y Wang F Wang Y Zhang X Zhao M Feng Q Wu J Zhao S Wu W Peng S
author_sort	Li S
title	Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis
title_short	Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis
title_full	Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis
title_fullStr	Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis
title_full_unstemmed	Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis
title_sort	small molecule pzl318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/abcc052591544c27a9d529ab6a9538db
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Small molecule PZL318: forming fluorescent nanoparticles capable of tracing their interactions with cancer cells and activated platelets, slowing tumor growth and inhibiting thrombosis

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