| Literature DB >> 24813696 |
James E Dahlman1,2,3, Carmen Barnes4, Omar Khan2,5, Aude Thiriot6, Siddharth Jhunjunwala2, Taylor E Shaw2, Yiping Xing2, Hendrik B Sager7, Gaurav Sahay2, Lauren Speciner4, Andrew Bader2, Roman L Bogorad2, Hao Yin2, Tim Racie4, Yizhou Dong2, Shan Jiang2, Danielle Seedorf2, Apeksha Dave2, Kamaljeet S Sandu2, Matthew J Webber2, Tatiana Novobrantseva4, Vera M Ruda2, Abigail K R Lytton-Jean2, Christopher G Levins2, Brian Kalish8, Dayna K Mudge8, Mario Perez9, Ludmila Abezgauz10, Partha Dutta7, Lynelle Smith9, Klaus Charisse4, Mark W Kieran6, Kevin Fitzgerald4, Matthias Nahrendorf7, Dganit Danino10, Rubin M Tuder9, Ulrich H von Andrian6, Akin Akinc4, Avi Schroeder11, Dipak Panigrahy6, Victor Kotelianski2, Robert Langer1,2,3,5, Daniel G Anderson1,2,3,5.
Abstract
Dysfunctional endothelium contributes to more diseases than any other tissue in the body. Small interfering RNAs (siRNAs) can help in the study and treatment of endothelial cells in vivo by durably silencing multiple genes simultaneously, but efficient siRNA delivery has so far remained challenging. Here, we show that polymeric nanoparticles made of low-molecular-weight polyamines and lipids can deliver siRNA to endothelial cells with high efficiency, thereby facilitating the simultaneous silencing of multiple endothelial genes in vivo. Unlike lipid or lipid-like nanoparticles, this formulation does not significantly reduce gene expression in hepatocytes or immune cells even at the dosage necessary for endothelial gene silencing. These nanoparticles mediate the most durable non-liver silencing reported so far and facilitate the delivery of siRNAs that modify endothelial function in mouse models of vascular permeability, emphysema, primary tumour growth and metastasis.Entities:
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Year: 2014 PMID： 24813696 PMCID： PMC4207430 DOI： 10.1038/nnano.2014.84
Source DB: PubMed Journal: Nat Nanotechnol ISSN： 1748-3387 Impact factor: 39.213