Dendrimer-Inspired Nanomaterials for the in Vivo Delivery of siRNA to Lung Vasculature
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Jacks_Dendrimer-Inspired Nanomaterials.pdf
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Author(s)
Barnes, Carmen M.
Khan, Omar Fizal
Zaia, Edmond
Jhunjhunwala, Siddharth
Xue, Wen
Yun, Dong Soo
Dahlman, James
Dong, Yizhou
Pelet, Jeisa
Webber, Matthew
Date Issued
December 2014
Journal
Nano Letters
Publisher
American Chemical Society (ACS)
Citation
Khan, Omar F. et al. “Dendrimer-Inspired Nanomaterials for the in Vivo Delivery of siRNA to Lung Vasculature.” Nano Letters 15.5 (2015): 3008–3016.
Version
Author's final manuscript
Abstract
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.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemical Engineering
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1021/nl5048972
