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Programmable Membrane-Mediated Attachment of Synthetic Virus-like Nanoparticles on Artificial Protocells for Enhanced Immunogenicity
Cell Reports Physical Science ( IF 8.9 ) Pub Date : 2021-01-06 , DOI: 10.1016/j.xcrp.2020.100291
Vincent Mukwaya , Peipei Zhang , Lingshan Liu , Auphedeous Yinme Dang-i , Mei Li , Stephen Mann , Hongjing Dou

The programming of protocells to implement and control the functions of living cells through activated membrane receptor signaling remains a challenge for the development of protoliving technologies. Here, we report a synthetic protocell capable of inducing high levels of macrophage activation in vitro. An immunogenic protocell comprising hyaluronic acid (HA)-polymer membrane decorated with synthetic virus-like particles derived from the functionalization of core-shell polymer nanoparticles with a Toll-like receptor agonist (Pam3SK4) and cell/protocell membrane-binding lectin (WGA) is fabricated. While the non-decorated HA-based protocells and functionalized SVLPs alone initiate moderate levels of macrophage activation, co-presentation of WGA and Pam3SK4 on the protocell membrane results in hyperactivation of the phagocytes via a synergistic multi-receptor process. This work offers opportunities for developing chemically programmable soft microscale agents capable of eliciting cellular signal transduction and genetic outputs and provides a step toward implementing future therapeutic strategies based on cognate interactions at the cell-protocell interface.



中文翻译:

可编程膜介导的合成病毒样纳米颗粒在人工原生细胞上的增强免疫原性的附着。

通过活化的膜受体信号传导对原细胞进行编程以实现和控制活细胞的功能仍然是原技术开发的一个挑战。在这里,我们报告了一种能够在体外诱导高水平巨噬细胞活化的合成原始细胞。一种免疫原性细胞,包括透明质酸(HA)-聚合物膜,该膜装饰有合成的病毒样颗粒,该颗粒衍生自具有Toll样受体激动剂(Pam3SK4)和细胞/原始细胞膜结合凝集素(WGA)的功能的核壳聚合物纳米颗粒是捏造的。虽然未修饰的基于HA的原始细胞和功能化的SVLP单独启动中等水平的巨噬细胞激活,但WGA和Pam3SK4在原始细胞膜上的共同呈递会通过协同的多受体过程导致吞噬细胞过度激活。

更新日期:2021-01-20
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