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Title of Journal: J Nanopart Res

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Abbravation: Journal of Nanoparticle Research

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Springer Netherlands

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DOI

10.1007/s10698-008-9057-2

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1572-896X

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Evaluation of the impact of chitosan/DNA nanoparti

Authors: Lanxia Liu Yuanyuan Bai Dunwan Zhu Liping Song Hai Wang Xia Dong Hailing Zhang Xigang Leng
Publish Date: 2010/11/28
Volume: 13, Issue: 6, Pages: 2577-2585
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Abstract

Chitosan CS is one of the most widely studied polymers in nonviral gene delivery since it is a cationic polysaccharide that forms nanoparticles with DNA and hence protects the DNA against digestion by DNase However the impact of CS/DNA nanoparticle on the immune system still remains poorly understood Previous investigations did not found CS/DNA nanoparticles had any significant impact on the function of human and murine macrophages To date little is known about the interaction between CS/DNA nanoparticles and naive CD4+ T cells This study was designed to investigate whether CS/DNA nanoparticles affect the initial differentiation direction of human naive CD4+ T cells The indirect impact of CS/DNA nanoparticles on naive CD4+ T cell differentiation was investigated by incubating the nanoparticles with human macrophage THP1 cells in one chamber of a transwell coincubation system with the enriched human naive CD4+ T cells being placed in the other chamber of the transwell The nanoparticles were also coincubated with the naive CD4+ T cells to explore their direct impact on naive CD4+ T cell differentiation by measuring the release of IL4 and IFNγ from the cells It was demonstrated that CS/DNA nanoparticles induced slightly elevated production of IL12 by THP1 cells possibly owing to the presence of CpG motifs in the plasmid However this macrophage stimulating activity was much less significant as compared with lipopolysaccharide and did not impact on the differentiation of the naive CD4+ T cells It was also demonstrated that when directly exposed to the naive CD4+ T cells the nanoparticles induced neither the activation of the naive CD4+ T cells in the absence of recombinant cytokines recombinant human IL4 or IFNγ that induce naive CD4+ T cell polarization nor any changes in the differentiation direction of naive CD4+ T cells in the presence of the corresponding cytokines

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