Cellular internalization and gene silencing of siRNA polyplexes by cytocleavable cationic polyrotaxanes with tailored rigid backbones.

Cellular internalization and gene silencing of siRNA polyplexes by cytocleavable cationic polyrotaxanes with tailored rigid backbones. Biomaterials. 2013 Mar;34(10):2480-91 Authors: Tamura A, Yui N Abstract To achieve successful delivery of siRNA therapeutics, cytocleavable cationic polyrotaxanes (PRXs) composed of N,N-dimethylaminoethyl (DMAE) group-modified α-cyclodextrins (CDs) that were threaded onto a poly(ethylene glycol) (PEG) axis and capped with a bulky stopper using cytocleavable disulfide linkages (DMAE-PRX) were utilized as an siRNA carrier. DMAE-PRXs with various numbers of threading CDs and modified DMAE groups were synthesized, and the physicochemical properties, cellular internalization, and gene silencing activity of DMAE-PRX/siRNA were investigated to elucidate the relationship between its supramolecular structure and its function. When the numbers of modified DMAE groups were increased, the DMAE-PRXs formed closely associated polyplexes with siRNA and increased their polyanion exchange resistance. Additionally, the DMAE-PRXs with 52 threading CDs (52CD-PRXs) showed greater binding capabilities with siRNA and greater resistance to polyanion competition than 31CD-PRXs, indicating that the highly CD-threaded PRX structure in the 52CD-PRXs is superior in forming stable polyplexes with siRNA. Indeed, 52CD-PRX/siRNA showed greater intracellular uptake of siRNA than 31CD-PRX/siRNA with comparable numbers of DMAE groups. 52CD-PRX/s...
Source: Biomaterials - Category: Materials Science Authors: Tags: Biomaterials Source Type: research