Anionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines

Ismaeil Haririan1,6, Mohammad Shafiee Alavidjeh1, Mohammad Reza Khorramizadeh2, Mehdi Shafiee Ardestani3, Zohre Zarei Ghane4, Hassan Namazi51Department of Pharmaceutics, Faculty of Pharmacy, 2Department of Medical Biotechnology, School of Advanced Medical Biotechnology, 3Department of Medicinal Chem...

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Autores principales:	Ismaeil Haririan, Mohammad Shafiee Alavidjeh, Mohammad Reza, et al
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2010
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/ae263484a1a34155b2afaff8a92103d1
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spelling	oai:doaj.org-article:ae263484a1a34155b2afaff8a92103d12021-12-02T05:02:08ZAnionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines1176-91141178-2013https://doaj.org/article/ae263484a1a34155b2afaff8a92103d12010-01-01T00:00:00Zhttp://www.dovepress.com/anionic-linear-globular-dendrimer-cis-platinum-ii-conjugates-promote-c-a3888https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Ismaeil Haririan1,6, Mohammad Shafiee Alavidjeh1, Mohammad Reza Khorramizadeh2, Mehdi Shafiee Ardestani3, Zohre Zarei Ghane4, Hassan Namazi51Department of Pharmaceutics, Faculty of Pharmacy, 2Department of Medical Biotechnology, School of Advanced Medical Biotechnology, 3Department of Medicinal Chemistry, Faculty of Pharmacy, 4Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; 5Faculty of Chemistry, Laboratory of Natural Carbohydrates and Biopolymer, University of Tabriz, Tabriz, Iran; 6Biomaterials Research Center (BRC), Tehran, IranAbstract: Due to their unique properties, Anticancer dendrimer-based drugs have been displaying promising results in both in vitro and in vivo in the treatment of cancerous cells, as compared to the traditional polymers. In this report, two conjugates (G1+Pt and G2+Pt) of cisplatin [cis-diaminedichloroplatinum; (CDDP)] with two generations (G1, G2) of a biocompatible anionic dendrimer were prepared in an aqueous media. Their potential cytotoxic effects, in two sensitive cancer cell lines HT1080 and CT26 together with one resistant cancer cell line SKOV3, using MTT (methyl thiazolyl tetrazolium) assay were examined. Hemolytic impacts and cell death mechanisms of the conjugates on human blood and HT1080 cell line were also investigated. The conjugate G2+Pt showed greater toxicity up to 9&times; and 2&times; in the sensitive and resistant cell lines (IC50 comparison, inhibitory concentration) respectively when compared to the parent drug. The G1+Pt conjugate showed greater toxicity only in the sensitive HT1080 (2&times;) and CT26 (3.7&times;) cell lines. Moreover, the G1+Pt conjugate was less toxic approximately one third of the cisplatin in SKOV3 after 48 hrs of incubation. In summary, the G2+Pt conjugate had greater toxicity than the G1+Pt conjugate and cisplatin, based on the in vitro results. Approximately the same hemolysis behavior was observed for both conjugates and cisplatin. Both apoptosis and necrosis mechanisms (about 2&times; more than cisplatin) were attributed to conjugates and cisplatin in a direct correlation between the concentration and the degree of cell death. In conclusion, these conjugates with such high potency and minimum hemolysis would be suitable candidates for use against these cancerous cell lines as efficient and novel antitumor agents.Keywords: cis-platinum (II), dendrimer, in vitro cytotoxicity, hemolysis, apoptosis-necrosis Ismaeil HaririanMohammad Shafiee AlavidjehMohammad Rezaet alDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2010, Iss default, Pp 63-75 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Ismaeil Haririan Mohammad Shafiee Alavidjeh Mohammad Reza et al Anionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines
description	Ismaeil Haririan1,6, Mohammad Shafiee Alavidjeh1, Mohammad Reza Khorramizadeh2, Mehdi Shafiee Ardestani3, Zohre Zarei Ghane4, Hassan Namazi51Department of Pharmaceutics, Faculty of Pharmacy, 2Department of Medical Biotechnology, School of Advanced Medical Biotechnology, 3Department of Medicinal Chemistry, Faculty of Pharmacy, 4Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; 5Faculty of Chemistry, Laboratory of Natural Carbohydrates and Biopolymer, University of Tabriz, Tabriz, Iran; 6Biomaterials Research Center (BRC), Tehran, IranAbstract: Due to their unique properties, Anticancer dendrimer-based drugs have been displaying promising results in both in vitro and in vivo in the treatment of cancerous cells, as compared to the traditional polymers. In this report, two conjugates (G1+Pt and G2+Pt) of cisplatin [cis-diaminedichloroplatinum; (CDDP)] with two generations (G1, G2) of a biocompatible anionic dendrimer were prepared in an aqueous media. Their potential cytotoxic effects, in two sensitive cancer cell lines HT1080 and CT26 together with one resistant cancer cell line SKOV3, using MTT (methyl thiazolyl tetrazolium) assay were examined. Hemolytic impacts and cell death mechanisms of the conjugates on human blood and HT1080 cell line were also investigated. The conjugate G2+Pt showed greater toxicity up to 9&times; and 2&times; in the sensitive and resistant cell lines (IC50 comparison, inhibitory concentration) respectively when compared to the parent drug. The G1+Pt conjugate showed greater toxicity only in the sensitive HT1080 (2&times;) and CT26 (3.7&times;) cell lines. Moreover, the G1+Pt conjugate was less toxic approximately one third of the cisplatin in SKOV3 after 48 hrs of incubation. In summary, the G2+Pt conjugate had greater toxicity than the G1+Pt conjugate and cisplatin, based on the in vitro results. Approximately the same hemolysis behavior was observed for both conjugates and cisplatin. Both apoptosis and necrosis mechanisms (about 2&times; more than cisplatin) were attributed to conjugates and cisplatin in a direct correlation between the concentration and the degree of cell death. In conclusion, these conjugates with such high potency and minimum hemolysis would be suitable candidates for use against these cancerous cell lines as efficient and novel antitumor agents.Keywords: cis-platinum (II), dendrimer, in vitro cytotoxicity, hemolysis, apoptosis-necrosis
format	article
author	Ismaeil Haririan Mohammad Shafiee Alavidjeh Mohammad Reza et al
author_facet	Ismaeil Haririan Mohammad Shafiee Alavidjeh Mohammad Reza et al
author_sort	Ismaeil Haririan
title	Anionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines
title_short	Anionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines
title_full	Anionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines
title_fullStr	Anionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines
title_full_unstemmed	Anionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines
title_sort	anionic linear-globular dendrimer-cis-platinum (ii) conjugates promote cytotoxicity in vitro against different cancer cell lines
publisher	Dove Medical Press
publishDate	2010
url	https://doaj.org/article/ae263484a1a34155b2afaff8a92103d1
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Anionic linear-globular dendrimer-cis-platinum (II) conjugates promote cytotoxicity in vitro against different cancer cell lines

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