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

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 moulded at the atomic level by chemical tailoring, 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, transfection efficiency in different cells was shown to be differently impacted by modifications on CDplex morphology, which has led to the identification of an optimal prototype for tissue‐selective DNA delivery to the spleen in vivo.

Authors:   Laura Gallego-Yerga, Juan M Benito, Laura Blanco-Fernández, María Martínez-Negro, Itziar Vélaz, Emilio Aicart, Elena Junquera, Carmen Ortiz Mellet, Conchita Tros de Ilarduya, Jose M. Garcia Fernandez
Journal:   Chemistry - A European Journal
Year:   2018
Pages:   n/a
DOI:   10.1002/chem.201705723
Publication date:   17-Jan-2018
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