Anti-epidermal growth factor receptor siRNA carried by chitosan-transacylated lipid nanocapsules increases sensitivity of glioblastoma cells to temozolomide

Khaled Messaoudi,1 Patrick Saulnier,1 Kim Boesen,1 Jean-Pierre Benoit,1,2 Frederic Lagarce1,21L'Université Nantes Angers Le Mans, INSERM U1066, Micro et nanomédecines biomimétiques, Angers, France; 2Pharmacy Department, Angers University Hospital, Angers, Fr...

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Autores principales:	Messaoudi K, Saulnier P, Boesen K, Benoit JP, Lagarce F
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/513877606eae4101ba3f7ada617ccd19
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spelling	oai:doaj.org-article:513877606eae4101ba3f7ada617ccd192021-12-02T04:54:04ZAnti-epidermal growth factor receptor siRNA carried by chitosan-transacylated lipid nanocapsules increases sensitivity of glioblastoma cells to temozolomide1178-2013https://doaj.org/article/513877606eae4101ba3f7ada617ccd192014-03-01T00:00:00Zhttp://www.dovepress.com/anti-epidermal-growth-factor-receptor-sirna-carried-by-chitosan-transa-a16205https://doaj.org/toc/1178-2013 Khaled Messaoudi,1 Patrick Saulnier,1 Kim Boesen,1 Jean-Pierre Benoit,1,2 Frederic Lagarce1,21L'Université Nantes Angers Le Mans, INSERM U1066, Micro et nanomédecines biomimétiques, Angers, France; 2Pharmacy Department, Angers University Hospital, Angers, FranceAbstract: Epidermal growth factor receptor (EGFR) is a crucial protein that plays an important role in the maintenance and development of glioblastomas. The silencing or knockdown of EGFR is possible by administering a small interfering ribonucleic acid (siRNA). Lipid nanocapsules (LNCs) covered by chitosan were developed in our laboratory by a transacylation process. The resulting nanocapsules have a positive zeta potential that enables electrostatic interactions with the negatively-charged siRNA. Prior to transfection, the cytotoxicity of the nanocapsules by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) test was performed on the U87MG cell line to determine non-toxic levels of the LNCs to avoid cell mortality. Treatment of the U87MG cells with the chitosan-transacylated LNCs/anti-EGFR siRNA complex resulted in a reduction of EGFR expression by 51.95%±6.03% (P≤0.05) after 96 hours of incubation. It also increased the cellular sensitivity to temozolomide in comparison to untreated cells with siRNA. The largest increase in mortality was 62.55%±3.55% (P<0.05). This successful knockdown provides proof for the concept of surface grafting of siRNA onto LNCs to modify cell sensitivity to temozolomide. The method could be implemented in future clinical models regarding the experimental treatment of glioblastoma cancer.Keywords: EGFR, glioblastoma, siRNA, lipid nanocapsules, chitosan, temozolomideMessaoudi KSaulnier PBoesen KBenoit JPLagarce FDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 1479-1490 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Messaoudi K Saulnier P Boesen K Benoit JP Lagarce F Anti-epidermal growth factor receptor siRNA carried by chitosan-transacylated lipid nanocapsules increases sensitivity of glioblastoma cells to temozolomide
description	Khaled Messaoudi,1 Patrick Saulnier,1 Kim Boesen,1 Jean-Pierre Benoit,1,2 Frederic Lagarce1,21L'Université Nantes Angers Le Mans, INSERM U1066, Micro et nanomédecines biomimétiques, Angers, France; 2Pharmacy Department, Angers University Hospital, Angers, FranceAbstract: Epidermal growth factor receptor (EGFR) is a crucial protein that plays an important role in the maintenance and development of glioblastomas. The silencing or knockdown of EGFR is possible by administering a small interfering ribonucleic acid (siRNA). Lipid nanocapsules (LNCs) covered by chitosan were developed in our laboratory by a transacylation process. The resulting nanocapsules have a positive zeta potential that enables electrostatic interactions with the negatively-charged siRNA. Prior to transfection, the cytotoxicity of the nanocapsules by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) test was performed on the U87MG cell line to determine non-toxic levels of the LNCs to avoid cell mortality. Treatment of the U87MG cells with the chitosan-transacylated LNCs/anti-EGFR siRNA complex resulted in a reduction of EGFR expression by 51.95%±6.03% (P≤0.05) after 96 hours of incubation. It also increased the cellular sensitivity to temozolomide in comparison to untreated cells with siRNA. The largest increase in mortality was 62.55%±3.55% (P<0.05). This successful knockdown provides proof for the concept of surface grafting of siRNA onto LNCs to modify cell sensitivity to temozolomide. The method could be implemented in future clinical models regarding the experimental treatment of glioblastoma cancer.Keywords: EGFR, glioblastoma, siRNA, lipid nanocapsules, chitosan, temozolomide
format	article
author	Messaoudi K Saulnier P Boesen K Benoit JP Lagarce F
author_facet	Messaoudi K Saulnier P Boesen K Benoit JP Lagarce F
author_sort	Messaoudi K
title	Anti-epidermal growth factor receptor siRNA carried by chitosan-transacylated lipid nanocapsules increases sensitivity of glioblastoma cells to temozolomide
title_short	Anti-epidermal growth factor receptor siRNA carried by chitosan-transacylated lipid nanocapsules increases sensitivity of glioblastoma cells to temozolomide
title_full	Anti-epidermal growth factor receptor siRNA carried by chitosan-transacylated lipid nanocapsules increases sensitivity of glioblastoma cells to temozolomide
title_fullStr	Anti-epidermal growth factor receptor siRNA carried by chitosan-transacylated lipid nanocapsules increases sensitivity of glioblastoma cells to temozolomide
title_full_unstemmed	Anti-epidermal growth factor receptor siRNA carried by chitosan-transacylated lipid nanocapsules increases sensitivity of glioblastoma cells to temozolomide
title_sort	anti-epidermal growth factor receptor sirna carried by chitosan-transacylated lipid nanocapsules increases sensitivity of glioblastoma cells to temozolomide
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/513877606eae4101ba3f7ada617ccd19
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Anti-epidermal growth factor receptor siRNA carried by chitosan-transacylated lipid nanocapsules increases sensitivity of glioblastoma cells to temozolomide

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