Dendrimer-Inspired Nanomaterials for the in Vivo Delivery of siRNA to Lung Vasculature
| العنوان: | Dendrimer-Inspired Nanomaterials for the in Vivo Delivery of siRNA to Lung Vasculature |
|---|---|
| المؤلفون: | Siddharth Jhunjhunwala, Robert Langer, Tyler Jacks, Edmond W. Zaia, Daniel G. Anderson, Carmen Barnes, Wen Xue, Jonathan K. Tsosie, Omar F. Khan, Wenxin Cai, Jeisa M. Pelet, Yizhou Dong, James E. Dahlman, Dong Soo Yun, Matthew J. Webber |
| المصدر: | Nano Letters. 15:3008-3016 |
| بيانات النشر: | American Chemical Society (ACS), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Dendrimers, Small interfering RNA, Materials science, Propylenimine, Bioengineering, Inflammation, Pharmacology, Article, Proinflammatory cytokine, In vivo, Dendrimer, medicine, Animals, Humans, General Materials Science, RNA, Small Interfering, Lung, Mechanical Engineering, Gene Transfer Techniques, Endothelial Cells, RNA, General Chemistry, Condensed Matter Physics, Nanostructures, medicine.anatomical_structure, RNA Interference, medicine.symptom |
| الوصف: | Targeted RNA delivery to lung endothelial cells has the potential to treat conditions that involve inflammation, such as chronic asthma and obstructive pulmonary disease. To this end, chemically modified dendrimer nanomaterials were synthesized and optimized for targeted small interfering RNA (siRNA) delivery to lung vasculature. Using a combinatorial approach, the free amines on multigenerational poly(amido amine) and poly(propylenimine) dendrimers were substituted with alkyl chains of increasing length. The top performing materials from in vivo screens were found to primarily target Tie2-expressing lung endothelial cells. At high doses, the dendrimer–lipid derivatives did not cause chronic increases in proinflammatory cytokines, and animals did not suffer weight loss due to toxicity. We believe these materials have potential as agents for the pulmonary delivery of RNA therapeutics. |
| تدمد: | 1530-6992 1530-6984 |
| DOI: | 10.1021/nl5048972 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5f240268a5242b386365482d078db229 https://doi.org/10.1021/nl5048972 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5f240268a5242b386365482d078db229 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306992 15306984 |
|---|---|
| DOI: | 10.1021/nl5048972 |