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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Main Authors: Guang Bai, Tong Xue, Xiaotao Dong, Uday Kumar Chinta, Jia Feng, Tuo Jin, Fei Wu
Format: Article
Language:English
Published: Elsevier 2020-05-01
Series:Asian Journal of Pharmaceutical Sciences
Subjects:
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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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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