Ionizable Amphiphilic Dendrimer-Based Nanomaterials with Alkyl-Chain-Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo
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Anderson_Ionizable amphiphilic.pdf
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Author(s)
Khan, Omar Fizal
Zaia, Edmond
Yin, Hao
Bogorad, Roman
Pelet, Jeisa
Webber, Matthew
Zhuang, Iris
Langer, Robert S
Anderson, Daniel Griffith
Dahlman, James E.
Date Issued
October 2014
Journal
Angewandte Chemie International Edition
Publisher
Wiley Blackwell
Citation
.Khan, Omar F. et al. “Ionizable Amphiphilic Dendrimer-Based Nanomaterials with Alkyl-Chain-Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo.” Angewandte Chemie International Edition 53.52 (2014): 14397–14401.
Version
Author's final manuscript
Abstract
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 multigenerational 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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1002/anie.201408221
