Zhu Rongrong, Zhu Yanjing, Zhang Min, Xiao Yu, Du Xiling, Liu Hui, Wang Shilong
Research Center for Translational Medicine at East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, PR China.
Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, PR China.
Mater Sci Eng C Mater Biol Appl. 2014 Jun 1;39:305-14. doi: 10.1016/j.msec.2014.03.005. Epub 2014 Mar 12.
Nanomaterials are increasingly used in many fields, including drug vectors and vaccine formulation. In this study, nano-TiO(2) and magnetic Fe(3)O(4)@TiO(2) were synthesized and their abilities to activate dendritic cells were investigated. The signaling pathway involved in their effects on the cellular functions was also explored. First, nano-TiO(2) and Fe(3)O(4)@TiO(2) were prepared with diameters of 82nm and 63nm, and zeta potentials of 41.5mV and 30.2mV, respectively. The magnetic property of Fe(3)O(4)@TiO(2) was detected to be 12.9emu/g. Both kinds of nanoparticles were proved to have good biocompatibility in vitro. Second, the exposure of nano-TiO2 and Fe(3)O(4)@TiO(2)caused an increased expression of TNF-α, CD86 and CD80, and besides, Fe(3)O(4)@TiO(2)showed a certain up-regulation on MHC-II. The cellular uptake of Ovalbumin on BMDCs could be strongly improved by nano-TiO2 and Fe(3)O(4)@TiO(2)as detected via flow cytometer and confocal observation. Further investigation revealed that nano-TiO(2) and Fe(3)O(4)@TiO(2)significantly increased the NF-κB expression in the nucleus, indicating that the NF-κB signaling pathway was involved in the dendritic cell maturation. Our results suggested that nano-TiO(2) and Fe(3)O(4)@TiO(2)may function as a useful vector to promote vaccine delivery in immune cells, and Fe(3)O(4)@TiO(2)provided a possibility to deliver and track vaccines via its magnetofection.
纳米材料在包括药物载体和疫苗制剂在内的许多领域中得到了越来越广泛的应用。在本研究中,合成了纳米二氧化钛(nano-TiO₂)和磁性四氧化三铁@二氧化钛(Fe₃O₄@TiO₂),并研究了它们激活树突状细胞的能力。还探索了其对细胞功能影响所涉及的信号通路。首先,制备的纳米TiO₂和Fe₃O₄@TiO₂直径分别为82nm和63nm,ζ电位分别为41.5mV和30.2mV。检测到Fe₃O₄@TiO₂的磁性为12.9emu/g。两种纳米颗粒在体外均被证明具有良好的生物相容性。其次,纳米TiO₂和Fe₃O₄@TiO₂的暴露导致肿瘤坏死因子-α(TNF-α)、CD86和CD80的表达增加,此外,Fe₃O₄@TiO₂对主要组织相容性复合体II类分子(MHC-II)有一定上调作用。通过流式细胞仪和共聚焦观察检测发现,纳米TiO₂和Fe₃O₄@TiO₂可显著提高骨髓来源树突状细胞(BMDCs)对卵清蛋白的细胞摄取。进一步研究表明,纳米TiO₂和Fe₃O₄@TiO₂显著增加了细胞核中核因子κB(NF-κB)的表达,表明NF-κB信号通路参与了树突状细胞的成熟。我们的结果表明,纳米TiO₂和Fe₃O₄@TiO₂可能作为一种有用的载体促进免疫细胞中的疫苗递送,并且Fe₃O₄@TiO₂通过其磁转染为疫苗递送和追踪提供了一种可能性。