Design and in vitro release study of siRNA loaded Layer by Layer nanoparticles with sustained gene silencing effect
Objectives: Clinical translation of siRNA therapeutics has been severely limited due to the lack of stable and sustained siRNA delivery systems. Furthermore, when nanocarrier systems with siRNA are administered systemically to treat diseases, insufficient doses reach the target tissue. Here we repor...
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sg-ntu-dr.10356-1406082020-06-01T10:43:37Z Design and in vitro release study of siRNA loaded Layer by Layer nanoparticles with sustained gene silencing effect Tan, Yang Fei Lee, Ying Shi Seet, Li-Fong Ng, Kee Woei Wong, Tina T. Venkatraman, Subbu School of Materials Science & Engineering NTU-Northwestern University Institute for Nanomedicine Engineering::Materials Layer-by-layer Nanoparticles siRNA Delivery Objectives: Clinical translation of siRNA therapeutics has been severely limited due to the lack of stable and sustained siRNA delivery systems. Furthermore, when nanocarrier systems with siRNA are administered systemically to treat diseases, insufficient doses reach the target tissue. Here we report the successful development of a new nanocarrier system for the management of fibrosis. Methods: The new carrier has a hydroxyapatite core, with alternating layers of siRNA and a cationic peptide. The siRNA used here targets secreted protein acidic and rich in cysteine (SPARC), a key matricellular protein involved in the regulation of collagen fibrillogenesis and assembly. We have also used FRET studies to elucidate the fate of the particles inside cells, including the mechanistic details of layer-by-layer detachment. Results: In vitro studies using murine conjunctiva fibroblasts show sustained release over 2 weeks, and that such released siRNA sustained SPARC knockdown without affecting cell growth, and maintained siRNA presence in the cells for at least two weeks with a single-dose treatment. Release studies of siRNA from particles in vitro gave insight on how the particles delivered prolonged gene-silencing effects. Conclusion: A single treatment of the layer-by-layer nanoparticle designed can achieve sustained gene silencing over 2 weeks. Localized delivery of stabilized siRNA with sustained-release capabilities opens the door for many other applications of siRNA-based gene regulation. NRF (Natl Research Foundation, S’pore) NMRC (Natl Medical Research Council, S’pore) MOH (Min. of Health, S’pore) 2020-06-01T02:05:15Z 2020-06-01T02:05:15Z 2018 Journal Article Tan, Y. F., Lee, Y. S., Seet, L.-F., Ng, K. W., Wong, T. T., & Venkatraman, S. (2018). Design and in vitro release study of siRNA loaded Layer by Layer nanoparticles with sustained gene silencing effect. Expert Opinion on Drug Delivery, 15(10), 937-949. doi:10.1080/17425247.2018.1518426 1742-5247 https://hdl.handle.net/10356/140608 10.1080/17425247.2018.1518426 30173580 2-s2.0-85053311837 10 15 937 949 en Expert Opinion on Drug Delivery © 2018 Informa UK Limited, trading as Taylor & Francis Group. All rights reserved. |
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Engineering::Materials Layer-by-layer Nanoparticles siRNA Delivery Tan, Yang Fei Lee, Ying Shi Seet, Li-Fong Ng, Kee Woei Wong, Tina T. Venkatraman, Subbu Design and in vitro release study of siRNA loaded Layer by Layer nanoparticles with sustained gene silencing effect |
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Objectives: Clinical translation of siRNA therapeutics has been severely limited due to the lack of stable and sustained siRNA delivery systems. Furthermore, when nanocarrier systems with siRNA are administered systemically to treat diseases, insufficient doses reach the target tissue. Here we report the successful development of a new nanocarrier system for the management of fibrosis. Methods: The new carrier has a hydroxyapatite core, with alternating layers of siRNA and a cationic peptide. The siRNA used here targets secreted protein acidic and rich in cysteine (SPARC), a key matricellular protein involved in the regulation of collagen fibrillogenesis and assembly. We have also used FRET studies to elucidate the fate of the particles inside cells, including the mechanistic details of layer-by-layer detachment. Results: In vitro studies using murine conjunctiva fibroblasts show sustained release over 2 weeks, and that such released siRNA sustained SPARC knockdown without affecting cell growth, and maintained siRNA presence in the cells for at least two weeks with a single-dose treatment. Release studies of siRNA from particles in vitro gave insight on how the particles delivered prolonged gene-silencing effects. Conclusion: A single treatment of the layer-by-layer nanoparticle designed can achieve sustained gene silencing over 2 weeks. Localized delivery of stabilized siRNA with sustained-release capabilities opens the door for many other applications of siRNA-based gene regulation. |
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School of Materials Science & Engineering |
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School of Materials Science & Engineering Tan, Yang Fei Lee, Ying Shi Seet, Li-Fong Ng, Kee Woei Wong, Tina T. Venkatraman, Subbu |
format |
Article |
author |
Tan, Yang Fei Lee, Ying Shi Seet, Li-Fong Ng, Kee Woei Wong, Tina T. Venkatraman, Subbu |
author_sort |
Tan, Yang Fei |
title |
Design and in vitro release study of siRNA loaded Layer by Layer nanoparticles with sustained gene silencing effect |
title_short |
Design and in vitro release study of siRNA loaded Layer by Layer nanoparticles with sustained gene silencing effect |
title_full |
Design and in vitro release study of siRNA loaded Layer by Layer nanoparticles with sustained gene silencing effect |
title_fullStr |
Design and in vitro release study of siRNA loaded Layer by Layer nanoparticles with sustained gene silencing effect |
title_full_unstemmed |
Design and in vitro release study of siRNA loaded Layer by Layer nanoparticles with sustained gene silencing effect |
title_sort |
design and in vitro release study of sirna loaded layer by layer nanoparticles with sustained gene silencing effect |
publishDate |
2020 |
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https://hdl.handle.net/10356/140608 |
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1681059383494049792 |