Polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells.
Polyethyleneimine modification of aluminum hydroxide nanoparticle enhances antigen transportation and cross-presentation of dendritic cells.
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氢氧化铝纳米颗粒的聚乙烯亚胺修饰增强树突状细胞的抗原运输和交叉呈递
DOI：
10.2147/ijn.s164097
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发表时间：
2018
影响因子：
8
通讯作者：
Mou Y
中科院分区：
文献类型：
--
作者：
Dong H;Wen ZF;Chen L;Zhou N;Liu H;Dong S;Hu HM;Mou Y
目的探讨聚乙烯亚胺（PEI）修饰的氢氧化铝纳米粒（LV@HPA/PEI）递送肿瘤抗原及增强树突状细胞（DC）抗原交叉递呈的可行性。材料与方法首先用PEI修饰LV@HPA纳米粒，然后观察LV@HPA/PEI对DC的影响。流式细胞术和Western blot检测卵清蛋白（OVA）在LV@HPA/PEI介导的DC中的表达。体外观察LV@HPA/PEI的生物相容性、DC的成熟度和抗原交叉提呈。将肿瘤来源的自噬体（DRibbles）与LV@HPA/PEI组合加载到DC中，并使用DC疫苗免疫小鼠。流式细胞仪检测免疫小鼠体内CD 3 + CD 8 +IFN-γ+ T细胞的百分率。此外，在携带PancO 2肿瘤的小鼠中体内检查LV@HPA/PEI-DRibble-DCs疫苗的功能特性。结果在我们的研究中，我们描述了如何LV@HPA/PEI可以是一个功能化的抗原递送系统，具有显着的抗原转运效果和可忽略的细胞毒性。发现LV@HPA/PEI可以容易地内化到DC中以辅助抗原释放到细胞质中。LV@HPA/PEI-OVA负载DC后，DC逐渐成熟，细胞因子IL-12的分泌和表面分子CD 80、CD 86的表达显著增加。有趣的是，负载有LV@HPA/PEI-DRibbles的DC可以促进鼠和人T细胞中肿瘤特异性T细胞的活化。在随后的体内实验中，LV@HPA/PEI-DRibble-DCs疫苗显著抑制肿瘤生长，提高了PancO 2荷瘤小鼠的存活率。结论成功构建了负载LV@ HPA/PEI纳米粒和肿瘤相关抗原的DCs自噬体高效抗肿瘤疫苗（DRibbles），为肿瘤免疫治疗提供了新的思路。
Background The aim of this study was to explore the feasibility of delivering tumor antigens and enhancing the antigen cross-presentation of dendritic cells (DCs) by aluminum hydroxide nanoparticle with polyethyleneimine (PEI) modification (LV@HPA/PEI). Materials and methods The LV@HPA nanoparticles were modified by PEI first, then the influence of LV@HPA/PEI on DCs was examined. The distinct expression of ovalbumin (OVA) protein transported into DCs by LV@HPA/PEI was observed by flow cytometry and Western blot. The biocompatibility of LV@HPA/PEI, maturity and antigen cross-presentation of DCs was observed in vitro. Tumor derived autophagosomes (DRibbles) combined with LV@HPA/PEI were loaded into DCs, and DC vaccines were used to immunize mice. The percentage of CD3+CD8+IFN-γ+ T cells in immunized mice was determined by flow cytometry. Additionally, the functional properties of the LV@HPA/PEI-DRibble-DCs vaccine were examined in vivo in PancO2 tumor-bearing mice. Results In our study, we described how LV@HPA/PEI can be a functionalized antigen delivery system with notable antigen transport effect and negligible cytotoxicity. It was found that LV@HPA/PEI could be easily internalized into DCs to assist antigen release into the cytoplasm. In addition, DCs matured gradually after loading with LV@HPA/PEI-OVA, which increased significantly the cytokine IL-12 secretion and expression of surface molecules CD80 and CD86. Interestingly, DCs loaded with LV@HPA/PEI-DRibbles could promote the activation of tumor-specific T cells both in murine and in human T cells. In the following in vivo experiments, the vaccine of LV@HPA/PEI-DRibble-DCs significantly inhibited tumor growth and improved the survival rate of the PancO2 tumor-bearing mice. Conclusion We established a high-performance anti-tumor vaccine of DCs loaded with LV@ HPA/PEI nanoparticles and tumor-associated antigens in autophagosomes (DRibbles), which could serve as a therapeutic strategy in cancer immunotherapy.