Dendrimer-Inspired Nanomaterials for the in Vivo Delivery of siRNA to Lung Vasculature
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; Tsosie, Jonathan; Jacks, Tyler E.; Langer, Robert S.; Anderson, Daniel Griffith; Cai, Wenxin,M. Arch.Massachusetts Institute of Technology.; ... Show more Show less
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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 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.
Date issued
2014-12Department
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 MITJournal
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
ISSN
1530-6984
1530-6992