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通过将阴离子脂质体掺入壳聚糖/DNA 复合物中增强抗龋 DNA 疫苗的鼻黏膜传递和免疫原性。

Enhanced nasal mucosal delivery and immunogenicity of anti-caries DNA vaccine through incorporation of anionic liposomes in chitosan/DNA complexes.

机构信息

National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, PR China.

出版信息

PLoS One. 2013 Aug 20;8(8):e71953. doi: 10.1371/journal.pone.0071953. eCollection 2013.

DOI:10.1371/journal.pone.0071953
PMID:23977186
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3748075/
Abstract

The design of optimized nanoparticles offers a promising strategy to enable DNA vaccines to cross various physiological barriers for eliciting a specific and protective mucosal immunity via intranasal administration. Here, we reported a new designed nanoparticle system through incorporating anionic liposomes (AL) into chitosan/DNA (CS/DNA) complexes. With enhanced cellular uptake, the constructed AL/CS/DNA nanoparticles can deliver the anti-caries DNA vaccine pGJA-P/VAX into nasal mucosa. TEM results showed the AL/CS/DNA had a spherical structure. High DNA loading ability and effective DNA protection against nuclease were proved by gel electrophoresis. The surface charge of the AL/CS/DNA depended strongly on pH environment, enabling the intracellular release of loaded DNA via a pH-mediated manner. In comparison to the traditional CS/DNA system, our new design rendered a higher transfection efficiency and longer residence time of the AL/CS/DNA at nasal mucosal surface. These outstanding features enable the AL/CS/DNA to induce a significantly (p<0.01) higher level of secretory IgA (SIgA) than the CS/DNA in animal study, and a longer-term mucosal immunity. On the other hand, the AL/CS/DNA exhibited minimal cytotoxicity. These results suggest that the developed nanoparticles offer a potential platform for DNA vaccine packaging and delivery for more efficient elicitation of mucosal immunity.

摘要

优化纳米颗粒的设计为通过鼻内给药使 DNA 疫苗跨越各种生理屏障以引发特定和保护性黏膜免疫提供了一种有前途的策略。在这里，我们通过将阴离子脂质体（AL）整合到壳聚糖/DNA（CS/DNA）复合物中，报道了一种新的纳米颗粒系统。通过增强细胞摄取，构建的 AL/CS/DNA 纳米颗粒可以将抗龋齿 DNA 疫苗 pGJA-P/VAX 递送到鼻黏膜中。TEM 结果表明 AL/CS/DNA 具有球形结构。凝胶电泳证明了 AL/CS/DNA 具有高的 DNA 负载能力和对核酸酶的有效 DNA 保护作用。AL/CS/DNA 的表面电荷强烈依赖于 pH 环境，能够通过 pH 介导的方式使负载的 DNA 在细胞内释放。与传统的 CS/DNA 系统相比，我们的新设计使 AL/CS/DNA 在鼻黏膜表面具有更高的转染效率和更长的停留时间。这些突出的特性使 AL/CS/DNA 能够在动物研究中诱导显著（p<0.01）更高水平的分泌型 IgA（SIgA），并产生更长期的黏膜免疫。另一方面，AL/CS/DNA 表现出最小的细胞毒性。这些结果表明，所开发的纳米颗粒为 DNA 疫苗的包装和递药提供了一个有潜力的平台，可更有效地引发黏膜免疫。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0ff9/3748075/ccbfcfc5bc0f/pone.0071953.g008.jpg
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