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In vivo endothelial siRNA delivery using polymeric nanoparticles with low molecular weight
- Source :
- PMC
- Publication Year :
- 2014
- Publisher :
- Springer Science and Business Media LLC, 2014.
-
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.<br />American Society for Engineering Education. National Defense Science and Engineering Graduate Fellowship<br />National Science Foundation (U.S.)<br />Massachusetts Institute of Technology. Presidential Fellowship
- Subjects :
- Small interfering RNA
Endothelium
Polymers
Biomedical Engineering
Bioengineering
Vascular permeability
Nanotechnology
Article
Cell Line
Mice
In vivo
RNA interference
Neoplasms
medicine
Animals
Humans
Gene silencing
General Materials Science
RNA, Small Interfering
Electrical and Electronic Engineering
Chemistry
Endothelial Cells
Condensed Matter Physics
Atomic and Molecular Physics, and Optics
Cell biology
medicine.anatomical_structure
Cell culture
Drug delivery
Nanoparticles
RNA Interference
Subjects
Details
- ISSN :
- 17483395 and 17483387
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Nature Nanotechnology
- Accession number :
- edsair.doi.dedup.....9ebc94f32b5adf1952001d9fb9a9ca6b