Dendrimer-Inspired Nanomaterials for the in Vivo Delivery of siRNA to Lung Vasculature
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...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
American Chemical Society (ACS)
2016
|
| Online Access: | http://hdl.handle.net/1721.1/105346 https://orcid.org/0000-0003-3811-2369 https://orcid.org/0000-0001-8046-2288 https://orcid.org/0000-0002-0460-8246 https://orcid.org/0000-0001-5786-0659 https://orcid.org/0000-0003-0624-3532 https://orcid.org/0000-0001-5785-8911 https://orcid.org/0000-0003-4255-0492 https://orcid.org/0000-0001-5629-4798 |
| Summary: | 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. |
|---|