Synthesis and evaluation of degradable polyurea block copolymers as siRNA delivery agents.

Clicks: 318
ID: 76280
2013
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Abstract
Chain extension by diisocyanate condensation provides a versatile and convenient means for preparing block copolymers. We have utilized this chemistry to prepare reducible multiblock polycations for siRNA delivery. This approach, an alternative to oxidative coupling, was suitable for preparing multiblock polycations with defined molecular weight and architecture. The polymer, PEG-b-multi-(polyhexylurea-co-oligo-L-lysine)-b-PEG, was capable of electrostatically condensing siRNA to form nano-sized polyplexes across a broad compositional range. We demonstrated that the polyplexes enter the cells via endocytosis and interact with the endosome membrane leading to destabilization and hence endosome escape. Another feature of these polymers is their multiple intra-chain disulfide linkages. This enables weakening of the polyplex via chain scission within the cytosol's reductive environment. In addition to the controlled preparation of the polymer, the polyplexes were capable of delivering siRNA in vitro to silence greater than 50% green fluorescent protein expression with negligible toxicity.
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Authors Cass, Peter;Knower, Warren;Hinton, Tracey;Shi, Shuning;Grusche, Felix;Tizard, Mark;Gunatillake, Pathiraja;
Journal Acta biomaterialia
Year 2013
DOI
10.1016/j.actbio.2013.05.011
URL
Keywords
delivery sirna polyurea polylysine reducible

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