Ionizable Amphiphilic Dendrimer-Based Nanomaterials with Alkyl-Chain-Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo
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 pol...
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| Format: | Article |
| Language: | en_US |
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Wiley Blackwell
2017
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| Online Access: | http://hdl.handle.net/1721.1/107199 https://orcid.org/0000-0003-3811-2369 https://orcid.org/0000-0001-6898-3793 https://orcid.org/0000-0003-0624-3532 https://orcid.org/0000-0003-4255-0492 https://orcid.org/0000-0001-5629-4798 |
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| author | Khan, Omar Fizal Zaia, Edmond Yin, Hao Bogorad, Roman Pelet, Jeisa Webber, Matthew Zhuang, Iris Langer, Robert S Anderson, Daniel Griffith Dahlman, James E. |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Khan, Omar Fizal Zaia, Edmond Yin, Hao Bogorad, Roman Pelet, Jeisa Webber, Matthew Zhuang, Iris Langer, Robert S Anderson, Daniel Griffith Dahlman, James E. |
| author_sort | Khan, Omar Fizal |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:07:58Z |
| format | Article |
| id | mit-1721.1/107199 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:07:58Z |
| publishDate | 2017 |
| publisher | Wiley Blackwell |
| record_format | dspace |
| spelling | mit-1721.1/1071992022-10-01T08:25:06Z Ionizable Amphiphilic Dendrimer-Based Nanomaterials with Alkyl-Chain-Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo Khan, Omar Fizal Zaia, Edmond Yin, Hao Bogorad, Roman Pelet, Jeisa Webber, Matthew Zhuang, Iris Langer, Robert S Anderson, Daniel Griffith Dahlman, James E. Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Khan, Omar Fizal Zaia, Edmond Yin, Hao Bogorad, Roman Pelet, Jeisa Webber, Matthew Zhuang, Iris Dahlman, James Langer, Robert S Anderson, Daniel Griffith 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. National Institutes of Health (U.S.) Centers of Cancer and Nanotechnology Excellence (Grant U54 CA151884) Armed Forces Institute of Regenerative Medicine (Grant W81XWH-08-2-0034) Alnylam Pharmaceuticals (Firm) 2017-03-06T21:03:36Z 2017-03-06T21:03:36Z 2014-10 2014-10 Article http://purl.org/eprint/type/JournalArticle 1433-7851 1521-3773 http://hdl.handle.net/1721.1/107199 .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. https://orcid.org/0000-0003-3811-2369 https://orcid.org/0000-0001-6898-3793 https://orcid.org/0000-0003-0624-3532 https://orcid.org/0000-0003-4255-0492 https://orcid.org/0000-0001-5629-4798 en_US http://dx.doi.org/10.1002/anie.201408221 Angewandte Chemie International Edition Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Wiley Blackwell PMC |
| spellingShingle | Khan, Omar Fizal Zaia, Edmond Yin, Hao Bogorad, Roman Pelet, Jeisa Webber, Matthew Zhuang, Iris Langer, Robert S Anderson, Daniel Griffith Dahlman, James E. Ionizable Amphiphilic Dendrimer-Based Nanomaterials with Alkyl-Chain-Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo |
| title | Ionizable Amphiphilic Dendrimer-Based Nanomaterials with Alkyl-Chain-Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo |
| title_full | Ionizable Amphiphilic Dendrimer-Based Nanomaterials with Alkyl-Chain-Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo |
| title_fullStr | Ionizable Amphiphilic Dendrimer-Based Nanomaterials with Alkyl-Chain-Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo |
| title_full_unstemmed | Ionizable Amphiphilic Dendrimer-Based Nanomaterials with Alkyl-Chain-Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo |
| title_short | Ionizable Amphiphilic Dendrimer-Based Nanomaterials with Alkyl-Chain-Substituted Amines for Tunable siRNA Delivery to the Liver Endothelium In Vivo |
| title_sort | ionizable amphiphilic dendrimer based nanomaterials with alkyl chain substituted amines for tunable sirna delivery to the liver endothelium in vivo |
| url | http://hdl.handle.net/1721.1/107199 https://orcid.org/0000-0003-3811-2369 https://orcid.org/0000-0001-6898-3793 https://orcid.org/0000-0003-0624-3532 https://orcid.org/0000-0003-4255-0492 https://orcid.org/0000-0001-5629-4798 |
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