Journal article
Combinatorial synthesis of chemically diverse core-shell nanoparticles for intracellular delivery
Proceedings of the National Academy of Sciences - PNAS, v 108(32), pp 12996-13001
09 Aug 2011
PMID: 21784981
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Combinatorial synthesis of chemically diverse core-shell nanoparticles for intracellular delivery
- Creators
- Daniel J. Siegwart - Massachusetts Institute of TechnologyKathryn A. Whitehead - Massachusetts Institute of TechnologyLutz Nuhn - Massachusetts Institute of TechnologyGaurav Sahay - Massachusetts Institute of TechnologyHao Cheng - Massachusetts Institute of TechnologyShan Jiang - Massachusetts Institute of TechnologyMinglin Ma - Massachusetts Institute of TechnologyAbigail Lytton-Jean - Koch Institute for Integrative Cancer Research At MITArturo Vegas - Massachusetts Institute of TechnologyPatrick Fenton - Massachusetts Institute of TechnologyChristopher G. Levins - Massachusetts Institute of TechnologyKevin T. Love - Massachusetts Institute of TechnologyHaeshin Lee - Massachusetts Institute of TechnologyChristina Cortez - Massachusetts Institute of TechnologySean P. Collins - Massachusetts Institute of TechnologyYing Fei Li - Massachusetts Institute of TechnologyJanice Jang - Massachusetts Institute of TechnologyWilliam Querbes - Alnylam Pharmaceuticals (United States)Christopher Zurenko - Alnylam Pharmaceuticals (United States)Tatiana Novobrantseva - Alnylam Pharmaceuticals (United States)Robert Langer - Massachusetts Institute of TechnologyDaniel G. Anderson - Massachusetts Institute of Technology
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 108(32), pp 12996-13001
- Publisher
- National Academy of Sciences
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Materials Science and Engineering
- Web of Science ID
- WOS:000293691400015
- Scopus ID
- 2-s2.0-80052010600
- Other Identifier
- 991021886374704721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Chemistry, Multidisciplinary