Plasmid‐Templated Control of DNA–Cyclodextrin Nanoparticle Morphology through Molecular Vector Design for Effective Gene Delivery

Plasmid‐Templated Control of DNA–Cyclodextrin Nanoparticle Morphology through Molecular... Engineering self‐assembled superstructures through complexation of plasmid DNA (pDNA) and single‐isomer nanometric size macromolecules (molecular nanoparticles) is a promising strategy for gene delivery. Notably, the functionality and overall architecture of the vector can be precisely molded at the atomic level by chemical tailoring, thereby enabling unprecedented opportunities for structure/self‐assembling/pDNA delivery relationship studies. Beyond this notion, by judiciously preorganizing the functional elements in cyclodextrin (CD)‐based molecular nanoparticles through covalent dimerization, here we demonstrate that the morphology of the resulting nanocomplexes (CDplexes) can be tuned, from spherical to ellipsoidal, rod‐type, or worm‐like nanoparticles, which makes it possible to gain understanding of their shape‐dependent transfection properties. The experimental findings are in agreement with a shift from chelate to cross‐linking interactions on going from primary‐face‐ to secondary‐face‐linked CD dimers, the pDNA partner acting as an active payload and as a template. Most interestingly, the transfection efficiency in different cells was shown to be differently impacted by modifications of the CDplex morphology, which has led to the identification of an optimal prototype for tissue‐selective DNA delivery to the spleen in vivo. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Chemistry - A European Journal Wiley

Plasmid‐Templated Control of DNA–Cyclodextrin Nanoparticle Morphology through Molecular Vector Design for Effective Gene Delivery

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
© 2018 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN
0947-6539
eISSN
1521-3765
D.O.I.
10.1002/chem.201705723
Publisher site
See Article on Publisher Site

Abstract

Engineering self‐assembled superstructures through complexation of plasmid DNA (pDNA) and single‐isomer nanometric size macromolecules (molecular nanoparticles) is a promising strategy for gene delivery. Notably, the functionality and overall architecture of the vector can be precisely molded at the atomic level by chemical tailoring, thereby enabling unprecedented opportunities for structure/self‐assembling/pDNA delivery relationship studies. Beyond this notion, by judiciously preorganizing the functional elements in cyclodextrin (CD)‐based molecular nanoparticles through covalent dimerization, here we demonstrate that the morphology of the resulting nanocomplexes (CDplexes) can be tuned, from spherical to ellipsoidal, rod‐type, or worm‐like nanoparticles, which makes it possible to gain understanding of their shape‐dependent transfection properties. The experimental findings are in agreement with a shift from chelate to cross‐linking interactions on going from primary‐face‐ to secondary‐face‐linked CD dimers, the pDNA partner acting as an active payload and as a template. Most interestingly, the transfection efficiency in different cells was shown to be differently impacted by modifications of the CDplex morphology, which has led to the identification of an optimal prototype for tissue‐selective DNA delivery to the spleen in vivo.

Journal

Chemistry - A European JournalWiley

Published: Jan 12, 2018

Keywords: ; ; ; ;

References

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