Assembling structurally customizable synthetic carriers of siRNA through thermodynamically self-regulated process
This study demonstrates that our previously reported polywraplex, a synthetic siRNA carrier consisting of a uni-molecular polyplex core of customizable size and a self-assembled tri-block copolymer envelop, may be constructed using dendrimers as the crosslinking junctions. Replacing the branched low...
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Format: | Article |
Language: | English |
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Elsevier
2020-05-01
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Series: | Asian Journal of Pharmaceutical Sciences |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S1818087618311577 |
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author | Guang Bai Tong Xue Xiaotao Dong Uday Kumar Chinta Jia Feng Tuo Jin Fei Wu |
author_facet | Guang Bai Tong Xue Xiaotao Dong Uday Kumar Chinta Jia Feng Tuo Jin Fei Wu |
author_sort | Guang Bai |
collection | DOAJ |
description | This study demonstrates that our previously reported polywraplex, a synthetic siRNA carrier consisting of a uni-molecular polyplex core of customizable size and a self-assembled tri-block copolymer envelop, may be constructed using dendrimers as the crosslinking junctions. Replacing the branched low molecular weight PEI with polyamidoamine (PAMAM) dendrimer in the zeta potential regulated polymerization resulted in the similar network structured cationic polymer with electron microscopically visible crosslinking junctions. This visibility may offer a convenient way to characterize the molecular structure of the rationally designed networked siRNA-packing cationic polymer without altering its chemical properties and biologic functions. A series of physical-chemical characterizations and biological assays, comprising size, zeta potential, pre-phagocytic siRNA leaking and degradation, and silencing of functional genes, confirmed that the advanced properties of polywraplexes remained with the dendrimer junctions. Although sixth generation PAMAM dendrimer was used as the crosslinking junctions in the size-customizable polymerization for electron microscopic observation, lower generation dendrimer should also work in case more practical and structurally defined cationic polymer is needed. |
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institution | Directory Open Access Journal |
issn | 1818-0876 |
language | English |
last_indexed | 2024-12-11T01:55:40Z |
publishDate | 2020-05-01 |
publisher | Elsevier |
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series | Asian Journal of Pharmaceutical Sciences |
spelling | doaj.art-5e62f2843ad1496b9335f88a107c95b52022-12-22T01:24:37ZengElsevierAsian Journal of Pharmaceutical Sciences1818-08762020-05-01153356364Assembling structurally customizable synthetic carriers of siRNA through thermodynamically self-regulated processGuang Bai0Tong Xue1Xiaotao Dong2Uday Kumar Chinta3Jia Feng4Tuo Jin5Fei Wu6School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaSchool of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaCorresponding authors. School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China. Tel.: +86 21 34204695.; School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaCorresponding authors. School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China. Tel.: +86 21 34204695.; School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, ChinaThis study demonstrates that our previously reported polywraplex, a synthetic siRNA carrier consisting of a uni-molecular polyplex core of customizable size and a self-assembled tri-block copolymer envelop, may be constructed using dendrimers as the crosslinking junctions. Replacing the branched low molecular weight PEI with polyamidoamine (PAMAM) dendrimer in the zeta potential regulated polymerization resulted in the similar network structured cationic polymer with electron microscopically visible crosslinking junctions. This visibility may offer a convenient way to characterize the molecular structure of the rationally designed networked siRNA-packing cationic polymer without altering its chemical properties and biologic functions. A series of physical-chemical characterizations and biological assays, comprising size, zeta potential, pre-phagocytic siRNA leaking and degradation, and silencing of functional genes, confirmed that the advanced properties of polywraplexes remained with the dendrimer junctions. Although sixth generation PAMAM dendrimer was used as the crosslinking junctions in the size-customizable polymerization for electron microscopic observation, lower generation dendrimer should also work in case more practical and structurally defined cationic polymer is needed.http://www.sciencedirect.com/science/article/pii/S1818087618311577Networked cationic polymerThermodynamically self-regulated processessiRNA deliveryUnimolecular polyplexZeta potential regulated polymerization |
spellingShingle | Guang Bai Tong Xue Xiaotao Dong Uday Kumar Chinta Jia Feng Tuo Jin Fei Wu Assembling structurally customizable synthetic carriers of siRNA through thermodynamically self-regulated process Asian Journal of Pharmaceutical Sciences Networked cationic polymer Thermodynamically self-regulated processes siRNA delivery Unimolecular polyplex Zeta potential regulated polymerization |
title | Assembling structurally customizable synthetic carriers of siRNA through thermodynamically self-regulated process |
title_full | Assembling structurally customizable synthetic carriers of siRNA through thermodynamically self-regulated process |
title_fullStr | Assembling structurally customizable synthetic carriers of siRNA through thermodynamically self-regulated process |
title_full_unstemmed | Assembling structurally customizable synthetic carriers of siRNA through thermodynamically self-regulated process |
title_short | Assembling structurally customizable synthetic carriers of siRNA through thermodynamically self-regulated process |
title_sort | assembling structurally customizable synthetic carriers of sirna through thermodynamically self regulated process |
topic | Networked cationic polymer Thermodynamically self-regulated processes siRNA delivery Unimolecular polyplex Zeta potential regulated polymerization |
url | http://www.sciencedirect.com/science/article/pii/S1818087618311577 |
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