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Assembling structurally customizable synthetic carriers of si RNA through thermodynamically self-regulated process

Assembling structurally customizable synthetic carriers of si RNA through thermodynamically self-regulated process

作     者:Guang Bai Tong Xue Xiaotao Dong Uday Kumar Chinta Jia Feng Tuo Jin Fei Wu Guang Bai;Tong Xue;Xiaotao Dong;Uday Kumar Chinta;Jia Feng;Tuo Jin;Fei Wu

作者机构:School of PharmacyShanghai Jiao Tong UniversityShanghai 200240China 

出 版 物:《Asian Journal of Pharmaceutical Sciences》 (亚洲药物制剂科学(英文))

年 卷 期:2020年第15卷第3期

页      面:356-364页

核心收录:

学科分类:1007[医学-药学(可授医学、理学学位)] 10[医学] 

基  金:the grant of the Natural Science Foundation of China(Grant nos.81373352 and 81690262) 

主  题:Networked cationic polymer Thermodynamically self-regulated processes siRNA delivery Unimolecular polyplex Zeta potential regulated polymerization 

摘      要: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 triblock 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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