Nanogel vaccines targeting dendritic cells: Contributions of the surface decoration and vaccine cargo on cell targeting and activation
Nanogel vaccines targeting dendritic cells: Contributions of the surface decoration and vaccine cargo on cell targeting and activation
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DOI：
10.1016/j.jconrel.2012.11.015
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发表时间：
2013-03-10
影响因子：
10.8
通讯作者：
McCullough, K. C.
中科院分区：
文献类型：
--
作者：
Thomann-Harwood, L. J.;Kaeuper, P.;McCullough, K. C.
树突状细胞 (DC) 在启动和促进免疫防御方面发挥着至关重要的作用，为疫苗提供了关键靶标。尽管基于纳米颗粒/纳米凝胶的递送载体显示出将疫苗递送至免疫系统的潜力，但关于它们与树突状细胞相互作用的特征的信息很少。虽然 DC 摄取颗粒已被证实，但细胞靶向机制尚未研究。此外，目前还不清楚颗粒表面修饰如何影响树突状细胞对此类疫苗的处理。因此，分析了携带模型抗原卵清蛋白 (ova) 的壳聚糖纳米凝胶与 DC 的相互作用和 DC 的加工。用藻酸盐 (alg) 或甘露糖化藻酸盐 (alg-man) 装饰的纳米凝胶表面用于靶向特定的 DC 受体。观察到颗粒的 DC 摄取，依赖于基于内体的过程。抑制 PI3 激酶或脂筏活性会损害摄取，而摄取只会减少，表明不止一种内吞途径参与；值得注意的是，在纳米凝胶递送或游离卵子中都观察到了这一点。重要的是，与起主要作用的卵子货物相比，颗粒的表面装饰对颗粒吸收的影响较小。迄今为止，疫苗货物的这种影响在很大程度上被忽视了。当与卵子直接相互作用的受体被阻断时，这会改变携带卵子的藻类纳米凝胶和藻类纳米凝胶的摄取。纳米凝胶确实具有影响力，因为 DC 功能活性的调节更多地归功于纳米凝胶结构。使用卵子特异性淋巴细胞进行体外再刺激测定，纳米凝胶递送的卵子和游离卵子在诱导特异性抗体方面同样有效。具有甘露糖表面修饰的纳米凝胶递送的卵子在诱导T淋巴细胞产生干扰素方面优于游离卵子。总之，数据表明，基于颗粒的疫苗输送应考虑表面装饰和疫苗货物的影响；每个都可以影响与 DC 相互作用的不同方面。这种综合影响可能会影响诱导的免疫反应的特征。 (C) 2012 Elsevier B.V. 保留所有权利。
Dendritic cells (DCs) play crucial roles in initiating and promoting immune defences, providing a pivotal target for vaccines. Although nanoparticle/nanogel-based delivery vehicles are showing potential for delivering vaccines to the immune system, there is little information on their characteristics of interaction with DCs. While particle uptake by DCs has been shown, the mechanism of cell targeting has not been studied. Moreover, it is still unclear how particle surface decoration influences the handling of such vaccines by DCs. Accordingly, chitosan nanogels carrying a model antigen, ovalbumin (ova), were analysed for interaction with and processing by DCs. Nanogel surfaces decorated with alginate (alg) or mannosylated alginate (alg-man), were used for targeting particular DC receptors. DC uptake of particles was observed, being dependent on endosomal-based processes. Inhibiting PI3-kinase or lipid raft activities impaired the uptake, which was only reduced, indicating the involvement of more than one endocytic pathway; notably, this was observed with both nanogel-delivered or free ova. Importantly, surface decoration of particles was less influential on particle uptake, contrasting with the ova cargo which played the major role. Such influence of the vaccine cargo has to date been largely ignored. When receptors interacting directly with ova were blocked, this altered the uptake of alg-nanogels and alg-man-nanogels carrying ova. The nanogels did have an influential role, in that modulation of DC functional activity owed more to the nanogel structure. Using an in vitro restimulation assay with ova-specific lymphocytes, nanogel-delivered and free ova were similarly effective at inducing specific antibody. Nanogel-delivered ova with mannose surface decoration was superior to free ova for inducing interferon-.production by T-lymphocytes. Together, the data demonstrates that particle-based vaccine delivery should consider the influences of both the surface decoration and the vaccine cargo; each can influence different aspects of the interaction with DCs. Such combined influences are likely to impinge on the characteristics of the immune response induced. (C) 2012 Elsevier B.V. All rights reserved.