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首页> 外文期刊>International Journal of Nanomedicine >Improved antigen cross-presentation by polyethyleneimine-based nanoparticles
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Improved antigen cross-presentation by polyethyleneimine-based nanoparticles

机译:聚乙烯亚胺基纳米颗粒改善了抗原交叉呈递

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Purpose: In the development of therapeutic vaccines against cancer, it is important to design strategies for antigen cross-presentation to stimulate cell-mediated immune responses against tumor antigens.Methods: We developed a polyethyleneimine (PEI)-based protein antigen delivery system to promote cross-presentation through the major histocompatibility complex (MHC) I pathway using ovalbumin (OVA) as a model antigen. PEIs formed nanoparticles with OVA by electrostatic interactions, as demonstrated by electrophoresis analysis, scanning electron microscopy, and photon correlation spectroscopy analysis.Results: The nanoparticles were used to stimulate mouse bone marrow-derived dendritic cells in vitro and resulted in significantly more OVA257–264/MHC I complex presentation on dendritic cell surfaces. The activated dendritic cells interacted specifically with RF33.70 to stimulate interleukin-2 secretion. The cross-presentation promoting effect was more prominent in dendritic cells that had been cultured for longer periods of time (13 days). Further studies comparing the antigen presentation efficacies by other polyanionic agents, such as PLL or lysosomotropic agents, suggested that the unique “proton sponge effect” of PEI facilitated antigen escape from the endosome toward the MHC I pathway.Conclusion: Such a PEI-based nanoparticle system may have the potential to be developed into an effective therapeutic vaccine delivery system.
机译:目的:在开发治疗癌症的疫苗中,重要的是设计抗原交叉呈递的策略,以刺激细胞介导的针对肿瘤抗原的免疫反应。方法:我们开发了基于聚乙烯亚胺(PEI)的蛋白质抗原递送系统,以促进使用卵清蛋白(OVA)作为模型抗原,通过主要组织相容性复合物(MHC)I途径进行交叉展示。电泳分析,扫描电子显微镜和光子相关光谱分析表明,PEIs通过静电相互作用形成了具有OVA的纳米颗粒。结果:该纳米颗粒可用于体外刺激小鼠骨髓来源的树突状细胞,并产生明显更多的OVA257-264 / MHC I在树突状细胞表面的复杂表现。活化的树突状细胞与RF33.70特异性相互作用,以刺激白介素2分泌。在培养时间较长(13天)的树突状细胞中,交叉展示促进作用更为突出。进一步比较其他聚阴离子试剂(例如PLL或溶溶同质剂)的抗原呈递效率的研究表明,PEI独特的“质子海绵效应”促进了抗原从内体向MHC I途径逸出。结论:这种基于PEI的纳米粒子该系统可能具有发展成为有效的治疗性疫苗递送系统的潜力。

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