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Bimodal Targeting of Human Leukocytes by Fc- and CpG-Decorated Polymersomes to Tune Immune Induction
Biomacromolecules ( IF 5.5 ) Pub Date : 2021-09-23 , DOI: 10.1021/acs.biomac.1c00985
Lucille F van Beek 1, 2 , Pascal L W Welzen 3 , Lisa U Teufel 1, 2 , Irma Joosten 1 , Dimitri A Diavatopoulos 1, 2 , Jan van Hest 3 , Marien I de Jonge 1, 2
Affiliation  

The use of well-defined nanovesicles composed of amphiphilic block copolymers (polymersomes) for delivery of adjuvants and antigens is a promising strategy for vaccine development. However, the potency of nanoparticle vaccines depends on efficient interaction with and activation of cells involved in antigen presentation, which can be achieved by targeting cellular receptors. Here, we showed that the Fc fragment display on the polymersome surface resulted in markedly improved interactions with granulocytes, monocytes, and NK cells, while for “naked” polymersomes, virtually no binding to leukocytes was observed. Moreover, CpG-decorated polymersomes were found to also interact with T and/or B cells. Interestingly, whole blood stimulations with Fc fragment and CpG-decorated polymersomes induced interleukin (IL)-6, IL-8, and TNF-α production, while naked polymersomes did not induce any cytokine production. In conclusion, specific immune induction by polymersomes can be controlled using bimodal targeting of different immune receptors, which is an essential feature for targeted vaccine delivery.

中文翻译:

通过 Fc 和 CpG 修饰的聚合物体对人白细胞进行双峰靶向以调节免疫诱导

使用由两亲性嵌段共聚物(聚合物体)组成的明确定义的纳米囊泡用于递送佐剂和抗原是疫苗开发的一种有前途的策略。然而,纳米颗粒疫苗的效力取决于与参与抗原呈递的细胞的有效相互作用和激活,这可以通过靶向细胞受体来实现。在这里,我们发现在聚合物囊泡表面展示的 Fc 片段显着改善了与粒细胞、单核细胞和 NK 细胞的相互作用,而对于“裸”聚合物囊泡,几乎没有观察到与白细胞的结合。此外,发现 CpG 修饰的聚合物囊泡也与 T 和/或 B 细胞相互作用。有趣的是,用 Fc 片段和 CpG 修饰的多聚体刺激全血会诱导白细胞介素 (IL)-6、IL-8 和 TNF-α 的产生,而裸聚合物体不会诱导任何细胞因子的产生。总之,可以使用不同免疫受体的双峰靶向来控制聚合物囊泡的特异性免疫诱导,这是靶向疫苗递送的基本特征。
更新日期:2021-10-12
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