Highly efficient siRNA delivery from core-shell mesoporous silica nanoparticles with multifunctional polymer caps
A new general route for siRNA delivery is presented combining porous core-shell silica nanocarriers with a modularly designed multifunctional block copolymer. Specifically, the internal storage and release of siRNA from mesoporous silica nanoparticles (MSN) with orthogonal core-shell surface chemistry was investigated as a function of pore-size, pore morphology, surface properties and pH. Very high siRNA loading capacities of up to 380 μg per mg MSN were obtained with charge-matched amino-functionalized mesoporous cores, and release profiles show up to 80% siRNA elution after 24 h. We demonstrate that adsorption and desorption of siRNA is mainly driven by electrostatic interactions, which allow for high loading capacities even in medium-sized mesopores with pore diameters down to 4 nm in a stellate pore morphology. The negatively charged MSN shell enabled the association with a block copolymer containing positively charged artificial amino acids and oleic acid blocks, which acts simultaneously as capping and endosomal release agent. The potential of this multifunctional delivery platform is demonstrated by highly effective cell transfection and siRNA delivery into KB-cells. A luciferase reporter gene knock-down of up to 80-90% was possible using extremely low cell exposures with only 2.5 μg MSN containing 0.5 μg siRNA per 100 μL well.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Nanoscale - 8(2016), 7 vom: 21. Feb., Seite 4007-19 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Möller, Karin [VerfasserIn] |
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| Links: |
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| Themen: |
7631-86-9 |
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| Anmerkungen: |
Date Completed 19.12.2016 Date Revised 30.12.2016 published: Print Citation Status MEDLINE |
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| doi: |
10.1039/c5nr06246b |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM256917205 |
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| 520 | |a A new general route for siRNA delivery is presented combining porous core-shell silica nanocarriers with a modularly designed multifunctional block copolymer. Specifically, the internal storage and release of siRNA from mesoporous silica nanoparticles (MSN) with orthogonal core-shell surface chemistry was investigated as a function of pore-size, pore morphology, surface properties and pH. Very high siRNA loading capacities of up to 380 μg per mg MSN were obtained with charge-matched amino-functionalized mesoporous cores, and release profiles show up to 80% siRNA elution after 24 h. We demonstrate that adsorption and desorption of siRNA is mainly driven by electrostatic interactions, which allow for high loading capacities even in medium-sized mesopores with pore diameters down to 4 nm in a stellate pore morphology. The negatively charged MSN shell enabled the association with a block copolymer containing positively charged artificial amino acids and oleic acid blocks, which acts simultaneously as capping and endosomal release agent. The potential of this multifunctional delivery platform is demonstrated by highly effective cell transfection and siRNA delivery into KB-cells. A luciferase reporter gene knock-down of up to 80-90% was possible using extremely low cell exposures with only 2.5 μg MSN containing 0.5 μg siRNA per 100 μL well | ||
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| 700 | 1 | |a Bräuchle, Christoph |e verfasserin |4 aut | |
| 700 | 1 | |a Wagner, Ernst |e verfasserin |4 aut | |
| 700 | 1 | |a Bein, Thomas |e verfasserin |4 aut | |
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