Journal
NANO LETTERS
Volume 15, Issue 5, Pages 3008-3016Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nl5048972
Keywords
siRNA; target lung endothelial cells; in vivo; modified dendrimer nanoparticles; nanomaterial
Categories
Funding
- 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
- American Association for Cancer Research
- Leukemia Lymphoma Society
- Juvenile Diabetes Research Fund
- NDSEG
- NSF GRFP
- MIT
- Mazumdar-Shaw Fellowship
- [1K99CA169512]
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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 king vasculature. Using a combinatorial, approach, the free amines on multigenerational poly(amida 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.
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