Barcoded nanoparticles for high throughput in vivo discovery of targeted therapeutics
Name
Dahlman-2017-Barcoded nanoparticles for high t.pdf
Size
1.16 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Kauffman, Kevin John
Xing, Yiping
Shaw, Taylor E.
Mir, Faryal
Dlott, Chloe C.
Langer, Robert S
Anderson, Daniel Griffith
Wang, Eric T
Dahlman, James E.
Date Issued
January 2017
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Dahlman, James E., et al. “Barcoded Nanoparticles for High Throughput in Vivo Discovery of Targeted Therapeutics.” Proceedings of the National Academy of Sciences, vol. 114, no. 8, Feb. 2017, pp. 2060–65. © 2017 National Academy of Sciences
Version
Final published version
Abstract
Nucleic acid therapeutics are limited by inefficient delivery to target tissues and cells and by an incomplete understanding of how nanoparticle structure affects biodistribution to off-target organs. Although thousands of nanoparticle formulations have been designed to deliver nucleic acids, most nanoparticles have been tested in cell culture contexts that do not recapitulate systemic in vivo delivery. To increase the number of nanoparticles that could be tested in vivo, we developed a method to simultaneously measure the biodistribution of many chemically distinct nanoparticles. We formulated nanoparticles to carry specific nucleic acid barcodes, administered the pool of particles, and quantified particle biodistribution by deep sequencing the barcodes. This method distinguished previously characterized lung- and liver- targeting nanoparticles and accurately reported relative quantities of nucleic acid delivered to tissues. Barcode sequences did not affect delivery, and no evidence of particle mixing was observed for tested particles. By measuring the biodistribution of 30 nanoparticles to eight tissues simultaneously, we identified chemical properties promoting delivery to some tissues relative to others. Finally, particles that distributed to the liver also silenced gene expression in hepatocytes when formulated with siRNA. This system can facilitate discovery of nanoparticles targeting specific tissues and cells and accelerate the study of relationships between chemical structure and delivery in vivo
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Harvard University--MIT Division of Health Sciences and Technology
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
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/10.1073/pnas.1620874114
