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

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 therapeuti...

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Autores principales: Prabhakar, Neeraj, Zhang, Jixi, Desai, Diti, Casals, Eudald, Gulin-Sarfraz, Tina, Näreoja, Tuomas, Westermarck, Jukka, Rosenholm, Jessica M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154729/
https://www.ncbi.nlm.nih.gov/pubmed/27994460
http://dx.doi.org/10.2147/IJN.S120611
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author Prabhakar, Neeraj
Zhang, Jixi
Desai, Diti
Casals, Eudald
Gulin-Sarfraz, Tina
Näreoja, Tuomas
Westermarck, Jukka
Rosenholm, Jessica M
author_facet Prabhakar, Neeraj
Zhang, Jixi
Desai, Diti
Casals, Eudald
Gulin-Sarfraz, Tina
Näreoja, Tuomas
Westermarck, Jukka
Rosenholm, Jessica M
author_sort Prabhakar, Neeraj
collection PubMed
description 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.
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spelling pubmed-51547292016-12-19 Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery Prabhakar, Neeraj Zhang, Jixi Desai, Diti Casals, Eudald Gulin-Sarfraz, Tina Näreoja, Tuomas Westermarck, Jukka Rosenholm, Jessica M Int J Nanomedicine Original Research 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. Dove Medical Press 2016-12-08 /pmc/articles/PMC5154729/ /pubmed/27994460 http://dx.doi.org/10.2147/IJN.S120611 Text en © 2016 Prabhakar et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Original Research
Prabhakar, Neeraj
Zhang, Jixi
Desai, Diti
Casals, Eudald
Gulin-Sarfraz, Tina
Näreoja, Tuomas
Westermarck, Jukka
Rosenholm, Jessica M
Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5154729/
https://www.ncbi.nlm.nih.gov/pubmed/27994460
http://dx.doi.org/10.2147/IJN.S120611
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