Potential antitumor activity of novel DODAC/PHO-S liposomes

Arthur Cássio de Lima Luna,1,2 Greice Kelle Viegas Saraiva,3 Otaviano Mendonça Ribeiro Filho,4 Gilberto Orivaldo Chierice,5 Salvador Claro Neto,5 Iolanda Midea Cuccovia,3 Durvanei Augusto Maria1,2 1Biochemistry and Biophysical Laboratory, Butantan Institute, 2Department of Med...

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Autores principales:	Luna ACL, Saraiva GKV, Filho OMR, Chierice GO, Neto SC, Cuccovia IM, Maria DA
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Hepatocellular carcinoma liposomes synthetic phosphoethanolamine tumor cells. Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/8b85249aca5a4712aba0e95f5937188d
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spelling	oai:doaj.org-article:8b85249aca5a4712aba0e95f5937188d2021-12-02T00:37:18ZPotential antitumor activity of novel DODAC/PHO-S liposomes1178-2013https://doaj.org/article/8b85249aca5a4712aba0e95f5937188d2016-04-01T00:00:00Zhttps://www.dovepress.com/potential-antitumor-activity-of-novel-dodacpho-s-liposomes-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Arthur Cássio de Lima Luna,1,2 Greice Kelle Viegas Saraiva,3 Otaviano Mendonça Ribeiro Filho,4 Gilberto Orivaldo Chierice,5 Salvador Claro Neto,5 Iolanda Midea Cuccovia,3 Durvanei Augusto Maria1,2 1Biochemistry and Biophysical Laboratory, Butantan Institute, 2Department of Medical Sciences, Medical School, 3Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, 4Environmental Health Surveillance, Municipality of Uberaba, Minas Gerais, 5Department of Chemistry and Molecular Physics, University of Sao Paulo, Sao Carlos, Brazil Abstract: In recent studies, we showed that synthetic phosphoethanolamine (PHO-S) has a great potential for inducing cell death in several tumor cell lines without damage to normal cells. However, its cytotoxic effect and selectivity against tumor cells could increase with encapsulation in cationic liposomes, such as dioctadecyldimethylammonium chloride (DODAC), due to electrostatic interactions between these liposomes and tumor cell membranes. Our aim was to use cationic liposomes to deliver PHO-S and to furthermore maximize the therapeutic effect of this compound. DODAC liposomes containing PHO-S (DODAC/PHO-S), at concentrations of 0.3–2.0 mM, prepared by ultrasonication, were analyzed by scanning electron microscopy (SEM) and dynamic light scattering. The cytotoxic effect of DODAC/PHO-S on B16F10 cells, Hepa1c1c7 cells, and human umbilical vein endothelial cells (HUVECs) was assessed by MTT assay. Cell cycle phases of B16F10 cells were analyzed by flow cytometry and the morphological changes by SEM, after treatment. The liposomes were spherical and polydisperse in solution. The liposomes were stable, presenting an average of ~50% of PHO-S encapsulation, with a small reduction after 40 days. DODAC demonstrated efficient PHO-S delivery, with the lowest values of IC50% (concentration that inhibits 50% of the growth of cells) for tumor cells, compared with PHO-S alone, with an IC50% value of 0.8 mM for B16F10 cells and 0.2 mM for Hepa1c1c7 cells, and without significant effects on endothelial cells. The Hepa1c1c7 cells showed greater sensitivity to the DODAC/PHO-S formulation when compared to B16F10 cells and HUVECs. The use of DODAC/PHO-S on B16F10 cells induced G2/M-phase cell cycle arrest, with the proportion significantly greater than that treated with PHO-S alone. The morphological analysis of B16F10 cells by SEM showed changes such as “bleb” formation, cell detachment, cytoplasmic retraction, and apoptotic bodies after DODAC/PHO-S treatment. Cationic liposomal formulation for PHO-S delivery promoted cytotoxicity more selectively and effectively against B16F10 and Hepa1c1c7 cells. Thus, the DODAC/PHO-S liposomal formulation presents great potential for preclinical studies.Keywords: hepatocellular carcinoma, lipossomal formulation, synthetic phosphoethanolamine, nanocarriers Luna ACLSaraiva GKVFilho OMRChierice GONeto SCCuccovia IMMaria DADove Medical PressarticleHepatocellular carcinomaliposomessynthetic phosphoethanolaminetumor cells.Medicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 1577-1591 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Hepatocellular carcinoma liposomes synthetic phosphoethanolamine tumor cells. Medicine (General) R5-920
spellingShingle	Hepatocellular carcinoma liposomes synthetic phosphoethanolamine tumor cells. Medicine (General) R5-920 Luna ACL Saraiva GKV Filho OMR Chierice GO Neto SC Cuccovia IM Maria DA Potential antitumor activity of novel DODAC/PHO-S liposomes
description	Arthur Cássio de Lima Luna,1,2 Greice Kelle Viegas Saraiva,3 Otaviano Mendonça Ribeiro Filho,4 Gilberto Orivaldo Chierice,5 Salvador Claro Neto,5 Iolanda Midea Cuccovia,3 Durvanei Augusto Maria1,2 1Biochemistry and Biophysical Laboratory, Butantan Institute, 2Department of Medical Sciences, Medical School, 3Department of Biochemistry, Institute of Chemistry, University of Sao Paulo, Sao Paulo, 4Environmental Health Surveillance, Municipality of Uberaba, Minas Gerais, 5Department of Chemistry and Molecular Physics, University of Sao Paulo, Sao Carlos, Brazil Abstract: In recent studies, we showed that synthetic phosphoethanolamine (PHO-S) has a great potential for inducing cell death in several tumor cell lines without damage to normal cells. However, its cytotoxic effect and selectivity against tumor cells could increase with encapsulation in cationic liposomes, such as dioctadecyldimethylammonium chloride (DODAC), due to electrostatic interactions between these liposomes and tumor cell membranes. Our aim was to use cationic liposomes to deliver PHO-S and to furthermore maximize the therapeutic effect of this compound. DODAC liposomes containing PHO-S (DODAC/PHO-S), at concentrations of 0.3–2.0 mM, prepared by ultrasonication, were analyzed by scanning electron microscopy (SEM) and dynamic light scattering. The cytotoxic effect of DODAC/PHO-S on B16F10 cells, Hepa1c1c7 cells, and human umbilical vein endothelial cells (HUVECs) was assessed by MTT assay. Cell cycle phases of B16F10 cells were analyzed by flow cytometry and the morphological changes by SEM, after treatment. The liposomes were spherical and polydisperse in solution. The liposomes were stable, presenting an average of ~50% of PHO-S encapsulation, with a small reduction after 40 days. DODAC demonstrated efficient PHO-S delivery, with the lowest values of IC50% (concentration that inhibits 50% of the growth of cells) for tumor cells, compared with PHO-S alone, with an IC50% value of 0.8 mM for B16F10 cells and 0.2 mM for Hepa1c1c7 cells, and without significant effects on endothelial cells. The Hepa1c1c7 cells showed greater sensitivity to the DODAC/PHO-S formulation when compared to B16F10 cells and HUVECs. The use of DODAC/PHO-S on B16F10 cells induced G2/M-phase cell cycle arrest, with the proportion significantly greater than that treated with PHO-S alone. The morphological analysis of B16F10 cells by SEM showed changes such as “bleb” formation, cell detachment, cytoplasmic retraction, and apoptotic bodies after DODAC/PHO-S treatment. Cationic liposomal formulation for PHO-S delivery promoted cytotoxicity more selectively and effectively against B16F10 and Hepa1c1c7 cells. Thus, the DODAC/PHO-S liposomal formulation presents great potential for preclinical studies.Keywords: hepatocellular carcinoma, lipossomal formulation, synthetic phosphoethanolamine, nanocarriers
format	article
author	Luna ACL Saraiva GKV Filho OMR Chierice GO Neto SC Cuccovia IM Maria DA
author_facet	Luna ACL Saraiva GKV Filho OMR Chierice GO Neto SC Cuccovia IM Maria DA
author_sort	Luna ACL
title	Potential antitumor activity of novel DODAC/PHO-S liposomes
title_short	Potential antitumor activity of novel DODAC/PHO-S liposomes
title_full	Potential antitumor activity of novel DODAC/PHO-S liposomes
title_fullStr	Potential antitumor activity of novel DODAC/PHO-S liposomes
title_full_unstemmed	Potential antitumor activity of novel DODAC/PHO-S liposomes
title_sort	potential antitumor activity of novel dodac/pho-s liposomes
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/8b85249aca5a4712aba0e95f5937188d
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Potential antitumor activity of novel DODAC/PHO-S liposomes

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