Click conjugated polymeric immuno-nanoparticles for targeted siRNA and antisense oligonucleotide delivery.

Click conjugated polymeric immuno-nanoparticles for targeted siRNA and antisense oligonucleotide delivery.
Biomaterials. 2013 Aug 7;
Authors: Chan DP, Deleavey GF, Owen SC, Damha MJ, Shoichet MS
Abstract
Efficient and targeted cellular delivery of small interfering RNAs (siRNAs) and antisense oligonucleotides (AONs) is a major challenge facing oligonucleotide-based therapeutics. The majority of current delivery strategies employ either conjugated ligands or oligonucleotide encapsulation within delivery vehicles to facilitate cellular uptake. Chemical modification of the oligonucleotides (ONs) can improve potency and duration of activity, usually as a result of improved nuclease resistance. Here we take advantage of innovations in both polymeric delivery vehicles and ON stabilization to achieve receptor-mediated targeted delivery of siRNAs or AONs for gene silencing. Polymeric nanoparticles comprised of poly(lactide-co-2-methyl, 2-carboxytrimethylene carbonate)-g-polyethylene glycol-furan/azide are click-modified with both anti-HER2 antibodies and nucleic acids on the exterior PEG corona. Phosphorothioate (PS), 2'F-ANA, and 2'F-RNA backbone chemical modifications improve siRNA and AON potency and duration of activity. Importantly, delivery of these nucleic acids on the exterior of the polymeric immuno-nanoparticles are as efficient in gene silencing as lipofectamine transfection without the associated potential toxicity of the latter.
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Source: Biomaterials - August 7, 2013 Category: Materials Science Authors: Chan DP, Deleavey GF, Owen SC, Damha MJ, Shoichet MS Tags: Biomaterials Source Type: research