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

• Published in: Asian journal of pharmceutical sciences Vol. 15; no. 3; pp. 356 - 364
• Main Authors: Bai, Guang, Xue, Tong, Dong, Xiaotao, Chinta, Uday Kumar, Feng, Jia, Jin, Tuo, Wu, Fei
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01-05-2020; Shenyang Pharmaceutical University; Elsevier
• Subjects: Networked cationic polymer; Research article; siRNA delivery; Thermodynamically self-regulated processes; Unimolecular polyplex; Zeta potential regulated polymerization; siRNA delivery; Zeta potential regulated polymerization; Networked cationic polymer; Unimolecular polyplex; Thermodynamically self-regulated processes
• ISSN: 1818-0876; 2221-285X
• DOI: 10.1016/j.ajps.2019.04.008

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.
[Display omitted] While synthetic carriers of nucleic acids have attracted intensive research efforts as reflected by hundreds thousands of reports to date, there has yet to be a therapeutically feasible one for systemic delivery due to the difficulty to functionalize synthetic carriers. The self-regulated assembly process shown in the present study may offer scientists in the field a highly reproducible yet easy-to-operate method to equip synthetic carriers with variety of functional components in precise load. We expect that more colleagues/peers in the community may love to use this system in their own studies.