The role of surface charge density in cationic liposome-promoted dendritic cell maturation and vaccine-induced immune responses
The role of surface charge density in cationic liposome-promoted dendritic cell maturation and vaccine-induced immune responses
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DOI：
10.1039/c1nr10166h
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发表时间：
2011-01-01
期刊：
影响因子：
6.7
通讯作者：
Cai, Lintao
中科院分区：
文献类型：
--
作者：
Ma, Yifan;Zhuang, Yan;Cai, Lintao
阳离子脂质体已成为一种新的佐剂和抗原递送系统，以提高疫苗的效力。然而，表面电荷密度在阳离子脂质体调节的免疫反应中的作用尚未阐明。在本研究中，我们将不同量的DOPC（一种中性脂质）掺入DOTAP（一种阳离子脂质）中，制备了一系列具有不同表面密度的DOTAP/DOPC阳离子脂质体。结果表明，DOTAP/DOPC阳离子脂质体调节的免疫应答依赖于表面电荷密度，并可能通过ROS信号传导发生。具有较高电荷密度的脂质体，如DOTAP/DOPC 5:0和4:1脂质体，可以有效地促进树突状细胞成熟、ROS生成、抗原摄取以及ova特异性IgG2a和ifn - γ的产生。相比之下，低电荷脂质体，如DOTAP/DOPC 1:4脂质体，即使在高浓度下也不能促进免疫应答，这证实了阳离子脂质体的免疫调节作用主要归因于其表面电荷密度。此外，DOTAP/DOPC 1:4脂质体在体内抑制抗ova抗体反应。总之，保持适当的表面电荷对于优化阳离子脂质体的佐剂效果和提高脂质体疫苗的效力至关重要。
Cationic liposomes have emerged as a novel adjuvant and antigen delivery system to enhance vaccine efficacy. However, the role of surface charge density in cationic liposome-regulated immune responses has not yet been elucidated. In the present study, we prepared a series of DOTAP/DOPC cationic liposomes with different surface densities by incorporating varying amounts of DOPC (a neutral lipid) into DOTAP (a cationic lipid). The results showed that DOTAP/DOPC cationic liposome-regulated immune responses relied on the surface charge density, and might occur through ROS signaling. The liposomes with a relatively high charge density, such as DOTAP/DOPC 5 : 0 and 4 : 1 liposomes, potently enhanced dendritic cell maturation, ROS generaion, antigen uptake, as well as the production of OVA-specific IgG2a and IFN-gamma. In contrast, low-charge liposomes, such as DOTAP/DOPC 1 : 4 liposome, failed to promote immune responses even at high concentrations, confirming that the immunoregulatory effect of cationic liposomes is mostly attributable to their surface charge density. Moreover, the DOTAP/DOPC 1 : 4 liposome suppressed anti-OVA antibody responses in vivo. Overall, maintaining an appropriate surface charge is crucial for optimizing the adjuvant effect of cationic liposomes and enhancing the efficacy of liposome-based vaccines.