Abstract
AbstractA synthetic carrier of small interfering RNA (siRNA) with customizable size, pH‐responsive degradability and optimized surface population of cell‐targeting agents is constructed precisely through a series of interlocked thermodynamically self‐regulated processes. This system consists of a unimolecular polyplex core formed from each individual molecule of networked cationic polymer and a multi‐functional shell assembled from a rationally designed triblock copolymer. The core‐forming polymer of defined size is synthesized via Zeta potential‐regulated condensation of branched and linear multi‐amine bearing oligomers through pH‐responding imidazole conjugated imine linkages. The shell‐forming copolymer consists of a multi‐carboxyl saccharide end block to guide to the surface assembly, a hydrophobic central block to form an encapsulating layer, and a poly(ethylene glycol) end block equipped with a highly selective active ester for “hooking” various cell‐targeting agents. Animal assays confirm the flexibility and convenience of this system to equip with selected functional components for systemic delivery of siRNA.
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