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Toll-like receptor-7 agonist decoration enhances the adjuvanticity of chitosan-DNA nanoparticles

Published in Journal of pharmaceutical sciences. 2012, vol. 101, no. 3, p. 1166-77
Abstract In order to provide an adjuvant-equipped carrier system for plasmid deoxyribonucleic acid (pDNA) vaccines, we grafted for the first time a Toll-like receptor (TLR)-7 agonistic moiety [9-benzyl-8-hydroxyadenine (HA)] through a poly(ethylene glycol) (PEG) spacer onto a water-soluble chitosan derivative [final copolymer: 6-0-carboxymethyl-N,N,N-trimethylchitosan (CTC)-graft-PEG-HA (CTCPHA)]. Successful grafting was confirmed by spectroscopic (H NMR, mass, ultraviolet-visible, and Fourier transform infrared spectroscopy) and chromatographic (size-exclusion chromatography-multi-angle laser light scattering) methods. In this article, TLR-7 agonist-decorated CTCPHA nanoparticles (NPs) were formulated by complex coacervation with pDNA expressing the green fluorescence protein. Resulting NPs had a size of around 200 nm with a positive surface charge and high DNA encapsulation efficiency. In contrast to the use of DNA alone, NP protected DNA against enzymatic degradation and enabled transfection of alveolar A549 cells. Interestingly, TLR-7 agonist decoration increased significantly the interleukin-8-related immune stimulatory capacity of polymeric chitosan and chitosan-based NP in human THP-1 macrophages when compared with controls. In summary, we demonstrate here the proof-of-principle that covalent TLR-7 agonist functionalization of chitosan-DNA NPs enhances the carrier's adjuvanticity, representing a valuable concept for future polymer-based DNA vaccination.
Keywords ChitosanNanoparticlesGenetic vaccinationNonviral gene deliveryMucosalt vaccinationVaccine adjuvantsToll-like receptor agonistTHP-1 macrophagesIL-8 release
PMID: 22190381
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HEUKING, Simon, BORCHARD, Gerrit. Toll-like receptor-7 agonist decoration enhances the adjuvanticity of chitosan-DNA nanoparticles. In: Journal of pharmaceutical sciences, 2012, vol. 101, n° 3, p. 1166-77. doi: 10.1002/jps.23017 https://archive-ouverte.unige.ch/unige:18731

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Deposited on : 2012-03-06

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