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

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 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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作者 Guang Bai [1] Tong Xue [1] Xiaotao Dong [1] Uday Kumar Chinta [1] Jia Feng [1] Tuo Jin [1] Fei Wu [1] 学术成果认领
作者单位 School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,China [1]
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DOI 10.1016/j.ajps.2019.04.008
发布时间 2024-09-02
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