Controlling Nanoparticle Uptake in Innate Immune Cells with Heparosan Polysaccharides.

Controlling Nanoparticle Uptake in Innate Immune Cells with Heparosan Polysaccharides.
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利用透明质酸多糖调控天然免疫细胞对纳米颗粒的摄取

DOI:
10.1021/acs.nanolett.2c02226
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发表时间:
2022-09-14
期刊:
影响因子:
10.8
通讯作者:
Wilhelm, Stefan
Wilhelm, Stefan
中科院分区:
材料科学1区
文献类型:
--
作者:
Yang, Wen;Frickenstein, Alex N.;Sheth, Vinit;Holden, Alyssa;Mettenbrink, Evan M.;Wang, Lin;Woodward, Alexis A.;Joo, Bryan S.;Butterfield, Sarah K.;Donahue, Nathan D.;Green, Dixy E.;Thomas, Abigail G.;Harcourt, Tekena;Young, Hamilton;Tang, Mulan;Malik, Zain A.;Harrison, Roger G.;Mukherjee, Priyabrata;DeAngelis, Paul L.;Wilhelm, Stefan

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我们使用肝素 (HEP) 多糖来控制纳米颗粒向先天免疫细胞的递送。我们的结果表明,先天免疫细胞通过网格蛋白介导的途径和巨胞饮途径以时间依赖性方式内吞 HEP 涂层的纳米颗粒。内吞作用后,我们在细胞内囊泡和细胞质中观察到 HEP 包被的纳米颗粒,证明纳​​米颗粒有可能从细胞内囊泡中逃逸。与其他糖胺聚糖类型的竞争仅部分抑制了 HEP 涂层纳米颗粒的内吞作用。我们进一步发现,通过系统地改变 HEP 表面密度,可以将纳米粒子摄取到先天免疫细胞中控制三个以上数量级。我们的结果表明,HEP 涂层纳米颗粒具有巨大的潜力,可以靶向先天免疫细胞,实现有效的细胞内递送,包括进入细胞质。这种 HEP 纳米粒子表面工程技术可广泛用于开发用于药物和基因传递以及基因编辑和免疫工程应用的高效纳米级装置。
We used heparosan (HEP) polysaccharides for controlling nanoparticle delivery to innate immune cells. Our results show that HEP-coated nanoparticles were endocytosed in a time-dependent manner by innate immune cells via both clathrin-mediated and macropinocytosis pathways. Upon endocytosis, we observed HEP-coated nanoparticles in intracellular vesicles and the cytoplasm, demonstrating the potential for nanoparticle escape from intracellular vesicles. Competition with other glycosaminoglycan types inhibited the endocytosis of HEP-coated nanoparticles only partially. We further found that nanoparticle uptake into innate immune cells can be controlled by more than three orders of magnitude via systematically varying the HEP surface density. Our results suggest a substantial potential for HEP-coated nanoparticles to target innate immune cells for efficient intracellular delivery, including into the cytoplasm. This HEP nanoparticle surface engineering technology may be broadly used to develop efficient nanoscale devices for drug and gene delivery as well as gene editing and immuno-engineering applications.
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