期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 53, 期 52, 页码 14397-14401出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201408221
关键词
amphiphiles; dendrimers; drug delivery; nanomaterials; RNA
资金
- National Institutes of Health Centers of Cancer and Nanotechnology Excellence [U54 CA151884]
- United States Army Medical Research and Materiel Command's Armed Forces Institute of Regenerative Medicine [W81XWH-08-2-0034]
- Alnylam Pharmaceuticals
- Alnylam
A library of dendrimers was synthesized and optimized for targeted small interfering RNA (siRNA) delivery to different cell subpopulations within the liver. Using a combinatorial approach, a library of these nanoparticle-forming materials was produced wherein the free amines on multi-generational poly(amido amine) and poly(propylenimine) dendrimers were substituted with alkyl chains of increasing length, and evaluated for their ability to deliver siRNA to liver cell subpopulations. Interestingly, two lead delivery materials could be formulated in a manner to alter their tissue tropism within the liver-with formulations from the same material capable of preferentially delivering siRNA to 1) endothelial cells, 2) endothelial cells and hepatocytes, or 3) endothelial cells, hepatocytes, and tumor cells in vivo. The ability to broaden or narrow the cellular destination of siRNA within the liver may provide a useful tool to address a range of liver diseases.
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