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Enhanced cytoplasmic delivery of siRNA using a stabilized polyion complex based on PEGylated nanogels with a cross-linked polyamine structure



Enhanced cytoplasmic delivery of siRNA using a stabilized polyion complex based on PEGylated nanogels with a cross-linked polyamine structure



Biomacromolecules 10(7): 1818-1827



A novel siRNA delivery system using a polyion complex (PIC) based on PEGylated polyamine nanogels composed of a chemically cross-linked poly[2-(N,N-diethylaminoethyl)methacrylate] (PDEAMA) core and surrounded by PEG tethered chains is described. The nanogel formed PIC spontaneously through electrostatic interaction upon mixing with siRNA. The nanogel/siRNA complex was characterized by a gel retardation assay, size and ΞΆ-potential measurements, and gene silencing activity using a cultured cell line. The nanogel/siRNA complexes showed higher polyanion exchange tolerability compared with the noncross-linked PEG-b-PDEAMA/siRNA complexes, indicating that the three-dimensionally cross-linked structure of the nanogel enhanced the stability of the PIC. Furthermore, the nanogel/siRNA complex was observed to undergo a remarkable enhancement of the gene silencing activity against the firefly luciferase gene expressed in HuH-7 cells at low N/P ratios (N/P = 2), whereas the noncross-linked PEG-b-PDEAMA/siRNA complexes showed negligible gene silencing activity. Moreover, confocal fluorescence microscopy revealed an efficient endosomal escape capability for the transportation of siRNAs into the cytoplasm, presumably due to the buffering effect of the PDEAMA core. Therefore, the PIC of siRNA with cross-linked polyamine nanogel is a potentially effective siRNA carrier for the development of in vivo therapeutic applications of siRNA.

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Accession: 052982995

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PMID: 19505137

DOI: 10.1021/bm900252d


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