School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Int J Nanomedicine. 2011 Jan 6;6:77-84. doi: 10.2147/IJN.S15457.
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.
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.
The nanoparticles were used to stimulate mouse bone marrow-derived dendritic cells in vitro and resulted in significantly more OVA(257-264)/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.
Such a PEI-based nanoparticle system may have the potential to be developed into an effective therapeutic vaccine delivery system.
在开发针对癌症的治疗性疫苗时，设计用于抗原交叉呈递的策略以刺激针对肿瘤抗原的细胞介导免疫应答非常重要。
我们开发了一种基于聚乙烯亚胺（PEI）的蛋白质抗原递呈系统，通过主要组织相容性复合物（MHC）I 途径促进交叉呈递，使用卵清蛋白（OVA）作为模型抗原。PEI 通过静电相互作用与 OVA 形成纳米颗粒，电泳分析、扫描电子显微镜和光子相关光谱分析均证明了这一点。
这些纳米颗粒用于体外刺激小鼠骨髓来源的树突状细胞，结果导致树突状细胞表面的 OVA（257-264）/MHC I 复合物呈递明显增加。经激活的树突状细胞与 RF33.70 特异性相互作用，刺激白细胞介素 2 的分泌。在培养时间更长（13 天）的树突状细胞中，这种促进交叉呈递的效果更为显著。进一步比较其他带负电荷的试剂（如 PLL 或溶酶体靶向试剂）的抗原呈递功效的研究表明，PEI 的独特“质子海绵效应”促进了抗原从内体向 MHC I 途径的逃逸。
这种基于 PEI 的纳米颗粒系统有可能被开发成有效的治疗性疫苗递送系统。
