Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery

Neeraj Prabhakar,1,2 Jixi Zhang,3 Diti Desai,1 Eudald Casals,1 Tina Gulin-Sarfraz,1 Tuomas Näreoja,2,4 Jukka Westermarck,5,6 Jessica M Rosenholm1 1Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 2Laboratory of Biophysics, Faculty of...

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Autores principales:	Prabhakar N, Zhang J, Desai D, Casals E, Gulin-Sarfraz T, Näreoja T, Westermarck J, Rosenholm JM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Mesoporous silica nanoparticles RNAi therapy siRNA delivery stimuli-responsive drug release hybrid nanocarriers Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/95f6e7558ae64098997c462b81f9b6c9
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spelling	oai:doaj.org-article:95f6e7558ae64098997c462b81f9b6c92021-12-02T06:32:32ZStimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery1178-2013https://doaj.org/article/95f6e7558ae64098997c462b81f9b6c92016-12-01T00:00:00Zhttps://www.dovepress.com/stimuli-responsive-hybrid-nanocarriers-developed-by-controllable-integ-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Neeraj Prabhakar,1,2 Jixi Zhang,3 Diti Desai,1 Eudald Casals,1 Tina Gulin-Sarfraz,1 Tuomas Näreoja,2,4 Jukka Westermarck,5,6 Jessica M Rosenholm1 1Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 2Laboratory of Biophysics, Faculty of Medicine, University of Turku, Turku, Finland; 3College of Bioengineering, Chongqing University, Chongqing, People’s Republic of China; 4Department of Neuroscience, Karolinska Institute, Stockholm, Sweden; 5Centre for Biotechnology, University of Turku and Åbo Akademi, 6Department of Pathology, University of Turku, Turku, Finland Abstract: Small interfering RNA (siRNA) is a highly potent drug in gene-based therapy with the challenge being to deliver it in a sustained manner. The combination of mesoporous silica nanoparticles (MSNs) and polycations in the confined pore space allows for incorporation and controlled release of therapeutic siRNA payloads. We hereby constructed MSNs with expanded mesopores and pore-surface-hyperbranched poly(ethyleneimine) (PEI) tethered with redox-cleavable linkers that could carry a high payload of siRNA (120 mg·g-1). The developed nanocarriers were efficiently taken up by cancer cells and were subsequently able to escape to the cytoplasm from the endosomes, most likely owing to the integrated PEI. Triggered by the intracellular redox conditions, the siRNA was sustainably released inside the cells over a period of several days. Functionality of siRNAs was demonstrated by using cell-killing siRNA as cargo. Despite not being the aim of the developed system, in vitro experiments using cell-killing siRNAs showed that the efficacy of siRNA transfection was comparable to the commercial in vitro transfection agent Lipofectamine. Consequently, the developed MSN-based delivery system offers a potential approach to hybrid nanocarriers for more efficient and long-term siRNA delivery and, in a longer perspective, in vivo gene silencing for RNA interference (RNAi) therapy. Keywords: mesoporous silica nanoparticles, RNAi therapy, siRNA delivery, stimuli-responsive drug release, hybrid nanocarriersPrabhakar NZhang JDesai DCasals EGulin-Sarfraz TNäreoja TWestermarck JRosenholm JMDove Medical PressarticleMesoporous silica nanoparticlesRNAi therapysiRNA deliverystimuli-responsive drug releasehybrid nanocarriersMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 6591-6608 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Mesoporous silica nanoparticles RNAi therapy siRNA delivery stimuli-responsive drug release hybrid nanocarriers Medicine (General) R5-920
spellingShingle	Mesoporous silica nanoparticles RNAi therapy siRNA delivery stimuli-responsive drug release hybrid nanocarriers Medicine (General) R5-920 Prabhakar N Zhang J Desai D Casals E Gulin-Sarfraz T Näreoja T Westermarck J Rosenholm JM Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery
description	Neeraj Prabhakar,1,2 Jixi Zhang,3 Diti Desai,1 Eudald Casals,1 Tina Gulin-Sarfraz,1 Tuomas Näreoja,2,4 Jukka Westermarck,5,6 Jessica M Rosenholm1 1Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, 2Laboratory of Biophysics, Faculty of Medicine, University of Turku, Turku, Finland; 3College of Bioengineering, Chongqing University, Chongqing, People’s Republic of China; 4Department of Neuroscience, Karolinska Institute, Stockholm, Sweden; 5Centre for Biotechnology, University of Turku and Åbo Akademi, 6Department of Pathology, University of Turku, Turku, Finland Abstract: Small interfering RNA (siRNA) is a highly potent drug in gene-based therapy with the challenge being to deliver it in a sustained manner. The combination of mesoporous silica nanoparticles (MSNs) and polycations in the confined pore space allows for incorporation and controlled release of therapeutic siRNA payloads. We hereby constructed MSNs with expanded mesopores and pore-surface-hyperbranched poly(ethyleneimine) (PEI) tethered with redox-cleavable linkers that could carry a high payload of siRNA (120 mg·g-1). The developed nanocarriers were efficiently taken up by cancer cells and were subsequently able to escape to the cytoplasm from the endosomes, most likely owing to the integrated PEI. Triggered by the intracellular redox conditions, the siRNA was sustainably released inside the cells over a period of several days. Functionality of siRNAs was demonstrated by using cell-killing siRNA as cargo. Despite not being the aim of the developed system, in vitro experiments using cell-killing siRNAs showed that the efficacy of siRNA transfection was comparable to the commercial in vitro transfection agent Lipofectamine. Consequently, the developed MSN-based delivery system offers a potential approach to hybrid nanocarriers for more efficient and long-term siRNA delivery and, in a longer perspective, in vivo gene silencing for RNA interference (RNAi) therapy. Keywords: mesoporous silica nanoparticles, RNAi therapy, siRNA delivery, stimuli-responsive drug release, hybrid nanocarriers
format	article
author	Prabhakar N Zhang J Desai D Casals E Gulin-Sarfraz T Näreoja T Westermarck J Rosenholm JM
author_facet	Prabhakar N Zhang J Desai D Casals E Gulin-Sarfraz T Näreoja T Westermarck J Rosenholm JM
author_sort	Prabhakar N
title	Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery
title_short	Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery
title_full	Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery
title_fullStr	Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery
title_full_unstemmed	Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery
title_sort	stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched pei with mesoporous silica nanoparticles for sustained intracellular sirna delivery
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/95f6e7558ae64098997c462b81f9b6c9
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Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery

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