Glucose-responsive mesoporous silica nanoparticles to generation of hydrogen peroxide for synergistic cancer starvation and chemistry therapy

Xiao Du,1 Tian Zhang,1 Guanglan Ma,1 Xiaochen Gu,2 Guangji Wang,3 Juan Li11Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, , People’s Republic of China; 2College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada; 3Center for New Drug Safet...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Du X, Zhang T, Ma G, Gu X, Wang G, Li J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Combination therapy Glucose oxidase Hyaluronic acid pH-sensitivity Nanomedicine Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c1001a40e879489fba1730757e6f7389
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:c1001a40e879489fba1730757e6f7389
record_format	dspace
spelling	oai:doaj.org-article:c1001a40e879489fba1730757e6f73892021-12-02T07:46:31ZGlucose-responsive mesoporous silica nanoparticles to generation of hydrogen peroxide for synergistic cancer starvation and chemistry therapy1178-2013https://doaj.org/article/c1001a40e879489fba1730757e6f73892019-04-01T00:00:00Zhttps://www.dovepress.com/glucose-responsive-mesoporous-silica-nanoparticles-to-generation-of-hy-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Xiao Du,1 Tian Zhang,1 Guanglan Ma,1 Xiaochen Gu,2 Guangji Wang,3 Juan Li11Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, , People’s Republic of China; 2College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada; 3Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, People’s Republic of ChinaBackground: The combination of novel starving therapy with chemotherapy is one of the most promising strategies to achieve an effective antitumor activity.Methods: Herein, we developed a multifunctional mesoporous silica nanoparticle (MSNs-GOx/PLL/HA) coated with poly (L-lysine) (PLL) and hyaluronic acid (HA) for co-delivery of glucose oxidase (GOx) and anticancer drug paclitaxel (PTX) for cancer treatment for the first time. Compared to single chemotherapy, introduction of GOx would not only selectively trigger the consumption of intracellular glucose, leading to the interruption of energy supply, but also elevat the endogenous H2O2 level, inducing stronger therapeutic effects.Results: The novel drug delivery system possessed desirable particle diameter of 40 nm and exhibited a pH-sensitive drug release behavior. An in vitro cellular uptake study indicated that MSNs-GOx/PLL/HA nanoparticles effectively enhanced the cellular uptake of drug in an apparently CD44 receptor-dependent manner, and delivered more cargo into cytoplasm via endolysosomal escape effect in presence of PLL. The nanoplatform has also demonstrated amplified synergistic therapeutic effects for remarkable tumor inhibition in a xenograft animal tumor model.Conclusion: Consequently, the developed synergistic starving-like/chemotherapy may provide a potential platform for next generation cancer therapy.Keywords: combination therapy, glucose oxidase, hyaluronic acid, pH-sensitivity, nanomedicineDu XZhang TMa GGu XWang GLi JDove Medical PressarticleCombination therapyGlucose oxidaseHyaluronic acidpH-sensitivityNanomedicineMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 2233-2251 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Combination therapy Glucose oxidase Hyaluronic acid pH-sensitivity Nanomedicine Medicine (General) R5-920
spellingShingle	Combination therapy Glucose oxidase Hyaluronic acid pH-sensitivity Nanomedicine Medicine (General) R5-920 Du X Zhang T Ma G Gu X Wang G Li J Glucose-responsive mesoporous silica nanoparticles to generation of hydrogen peroxide for synergistic cancer starvation and chemistry therapy
description	Xiao Du,1 Tian Zhang,1 Guanglan Ma,1 Xiaochen Gu,2 Guangji Wang,3 Juan Li11Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, , People’s Republic of China; 2College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada; 3Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, People’s Republic of ChinaBackground: The combination of novel starving therapy with chemotherapy is one of the most promising strategies to achieve an effective antitumor activity.Methods: Herein, we developed a multifunctional mesoporous silica nanoparticle (MSNs-GOx/PLL/HA) coated with poly (L-lysine) (PLL) and hyaluronic acid (HA) for co-delivery of glucose oxidase (GOx) and anticancer drug paclitaxel (PTX) for cancer treatment for the first time. Compared to single chemotherapy, introduction of GOx would not only selectively trigger the consumption of intracellular glucose, leading to the interruption of energy supply, but also elevat the endogenous H2O2 level, inducing stronger therapeutic effects.Results: The novel drug delivery system possessed desirable particle diameter of 40 nm and exhibited a pH-sensitive drug release behavior. An in vitro cellular uptake study indicated that MSNs-GOx/PLL/HA nanoparticles effectively enhanced the cellular uptake of drug in an apparently CD44 receptor-dependent manner, and delivered more cargo into cytoplasm via endolysosomal escape effect in presence of PLL. The nanoplatform has also demonstrated amplified synergistic therapeutic effects for remarkable tumor inhibition in a xenograft animal tumor model.Conclusion: Consequently, the developed synergistic starving-like/chemotherapy may provide a potential platform for next generation cancer therapy.Keywords: combination therapy, glucose oxidase, hyaluronic acid, pH-sensitivity, nanomedicine
format	article
author	Du X Zhang T Ma G Gu X Wang G Li J
author_facet	Du X Zhang T Ma G Gu X Wang G Li J
author_sort	Du X
title	Glucose-responsive mesoporous silica nanoparticles to generation of hydrogen peroxide for synergistic cancer starvation and chemistry therapy
title_short	Glucose-responsive mesoporous silica nanoparticles to generation of hydrogen peroxide for synergistic cancer starvation and chemistry therapy
title_full	Glucose-responsive mesoporous silica nanoparticles to generation of hydrogen peroxide for synergistic cancer starvation and chemistry therapy
title_fullStr	Glucose-responsive mesoporous silica nanoparticles to generation of hydrogen peroxide for synergistic cancer starvation and chemistry therapy
title_full_unstemmed	Glucose-responsive mesoporous silica nanoparticles to generation of hydrogen peroxide for synergistic cancer starvation and chemistry therapy
title_sort	glucose-responsive mesoporous silica nanoparticles to generation of hydrogen peroxide for synergistic cancer starvation and chemistry therapy
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/c1001a40e879489fba1730757e6f7389
work_keys_str_mv	AT dux glucoseresponsivemesoporoussilicananoparticlestogenerationofhydrogenperoxideforsynergisticcancerstarvationandchemistrytherapy AT zhangt glucoseresponsivemesoporoussilicananoparticlestogenerationofhydrogenperoxideforsynergisticcancerstarvationandchemistrytherapy AT mag glucoseresponsivemesoporoussilicananoparticlestogenerationofhydrogenperoxideforsynergisticcancerstarvationandchemistrytherapy AT gux glucoseresponsivemesoporoussilicananoparticlestogenerationofhydrogenperoxideforsynergisticcancerstarvationandchemistrytherapy AT wangg glucoseresponsivemesoporoussilicananoparticlestogenerationofhydrogenperoxideforsynergisticcancerstarvationandchemistrytherapy AT lij glucoseresponsivemesoporoussilicananoparticlestogenerationofhydrogenperoxideforsynergisticcancerstarvationandchemistrytherapy
_version_	1718399182888239104

Glucose-responsive mesoporous silica nanoparticles to generation of hydrogen peroxide for synergistic cancer starvation and chemistry therapy

Ejemplares similares