Combinatorial synthesis of chemically diverse core-shell nanoparticles for intracellular delivery
Name
Siegwart-2011-Aug-Combinatorial synthe.pdf
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Author(s)
Whitehead, Kathryn Ann
Nuhn, Lutz
Sahay, Gaurav
Cheng, Hao
Jiang, Shan
Ma, Minglin
Lytton-Jean, Abigail K. R.
Vegas, Arturo
Fenton, Patrick
Levins, Christopher G.
Date Issued
August 2011
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences (U.S.)
Citation
Siegwart, D. J. et al. “Combinatorial Synthesis of Chemically Diverse Core-shell Nanoparticles for Intracellular Delivery.” Proceedings of the National Academy of Sciences 108.32 (2011): 12996–13001. Web.
Version
Final published version
Abstract
Analogous to an assembly line, we employed a modular design for the high-throughput study of 1,536 structurally distinct nanoparticles with cationic cores and variable shells. This enabled elucidation of complexation, internalization, and delivery trends that could only be learned through evaluation of a large library. Using robotic automation, epoxide-functionalized block polymers were combinatorially cross-linked with a diverse library of amines, followed by measurement of molecular weight, diameter, RNA complexation, cellular internalization, and in vitro siRNA and pDNA delivery. Analysis revealed structure-function relationships and beneficial design guidelines, including a higher reactive block weight fraction, stoichiometric equivalence between epoxides and amines, and thin hydrophilic shells. Cross-linkers optimally possessed tertiary dimethylamine or piperazine groups and potential buffering capacity. Covalent cholesterol attachment allowed for transfection in vivo to liver hepatocytes in mice. The ability to tune the chemical nature of the core and shell may afford utility of these materials in additional applications.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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/10.1073/pnas.1106379108
