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透明质酸包覆壳聚糖纳米粒降低了形成的蛋白冠的免疫原性。

Hyaluronic Acid Coated Chitosan Nanoparticles Reduced the Immunogenicity of the Formed Protein Corona.

机构信息

National Center for Biotechnology, Life science and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST), P.O. Box 6086, Riyadh, 11461, Saudi Arabia.

Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, P.O. Box 2925, Riyadh, 11461, Saudi Arabia.

出版信息

Sci Rep. 2017 Sep 5;7(1):10542. doi: 10.1038/s41598-017-10836-7.

DOI:10.1038/s41598-017-10836-7
PMID:28874846
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5585335/
Abstract

Studying the interactions of nanoparticles (NPs) with serum proteins is necessary for the rational development of nanocarriers. Optimum surface chemistry is a key consideration to modulate the formation of the serum protein corona (PC) and the resultant immune response. We investigated the constituent of the PC formed by hyaluronic acid-coated chitosan NPs (HA-CS NPs). Non-decorated chitosan NPs (CS NPs) and alginate-coated chitosan NPs (Alg-CS NPs) were utilized as controls. Results show that HA surface modifications significantly reduced protein adsorption relative to controls. Gene Ontology analysis demonstrates that HA-CS NPs were the least immunogenic nanocarriers. Indeed, less inflammatory proteins were adsorbed onto HA-CS NPs as opposed to CS and Alg-CS NPs. Interestingly, HA-CS NPs differentially adsorbed two unique anti-inflammatory proteins (ITIH4 and AGP), which were absent from the PC of both controls. On the other hand, CS and Alg-CS NPs selectively adsorbed a proinflammatory protein (Clusterin) that was not found on the surfaces of HA-CS NPs. While further studies are needed to investigate abilities of the PCs of only ITIH4 and AGP to modulate the interaction of NPs with the host immune system, our results suggest that this proof-of-concept could potentially be utilized to reduce the immunogenicity of a wide range of nanomaterials.

摘要

研究纳米粒子(NPs)与血清蛋白的相互作用对于合理开发纳米载体是必要的。最佳的表面化学修饰是调节血清蛋白冠(PC)形成和由此产生的免疫反应的关键考虑因素。我们研究了透明质酸包覆壳聚糖 NPs(HA-CS NPs)形成的 PC 的组成。未修饰的壳聚糖 NPs(CS NPs)和藻酸盐包覆壳聚糖 NPs(Alg-CS NPs)被用作对照。结果表明,HA 表面修饰显著降低了相对对照的蛋白质吸附。GO 分析表明,HA-CS NPs 是免疫原性最低的纳米载体。事实上,与 CS 和 Alg-CS NPs 相比,HA-CS NPs 上吸附的炎症蛋白较少。有趣的是,HA-CS NPs 差异吸附了两种独特的抗炎蛋白(ITIH4 和 AGP),而这两种蛋白不存在于两种对照的 PC 中。另一方面,CS 和 Alg-CS NPs 选择性吸附了一种炎症蛋白(Clusterin),而在 HA-CS NPs 表面没有发现这种蛋白。虽然需要进一步研究仅 ITIH4 和 AGP 的 PCs 调节 NPs 与宿主免疫系统相互作用的能力,但我们的结果表明,这一概念验证可能被用于降低广泛纳米材料的免疫原性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e147/5585335/904860aac740/41598_2017_10836_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e147/5585335/0b702af79bb9/41598_2017_10836_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e147/5585335/904860aac740/41598_2017_10836_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e147/5585335/0b702af79bb9/41598_2017_10836_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e147/5585335/904860aac740/41598_2017_10836_Fig4_HTML.jpg

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