Gold Nanorods Induce Endoplasmic Reticulum Stress and Autocrine Inflammatory Activation in Human Neutrophils,ACS Nano

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Gold Nanorods Induce Endoplasmic Reticulum Stress and Autocrine Inflammatory Activation in Human Neutrophils
ACS Nano ( IF 15.8 ) Pub Date : 2022-06-23 , DOI: 10.1021/acsnano.2c03586
Ronja Schirrmann ₁ , Michael Erkelenz ₂ , Kim Lamers ₁ , Oliver Sritharan ₂ , Milen Nachev ₃ , Bernd Sures ₃ , Sebastian Schlücker _{2,

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Affiliation

Gold nanorods (AuNRs) are promising agents for diverse biomedical applications such as drug and gene delivery, bioimaging, and cancer treatment. Upon in vivo application, AuNRs quickly interact with cells of the immune system. On the basis of their strong intrinsic phagocytic activity, polymorphonuclear neutrophils (PMNs) are specifically equipped for the uptake of particulate materials such as AuNRs. Therefore, understanding the interaction of AuNRs with PMNs is key for the development of safe and efficient therapeutic applications. In this study, we investigated the uptake, intracellular processing, and cell biological response induced by AuNRs in PMNs. We show that uptake of AuNRs mainly occurs via phagocytosis and macropinocytosis with rapid deposition of AuNRs in endosomes within 5 min. Within 60 min, AuNR uptake induced an unfolded protein response (UPR) along with induction of inositol-requiring enzyme 1 α (IREα) and features of endoplasmic reticulum (ER) stress. This early response was followed by a pro-inflammatory autocrine activation loop that involves LOX1 upregulation on the cell surface and increased secretion of IL8 and MMP9. Our study provides comprehensive mechanistic insight into the interaction of AuNRs with immune cells and suggests potential targets to limit the unwanted immunopathological activation of PMNs during application of AuNRs.

中文翻译：

金纳米棒诱导人中性粒细胞内质网应激和自分泌炎症激活

金纳米棒 (AuNR) 是用于多种生物医学应用（例如药物和基因递送、生物成像和癌症治疗）的有前途的试剂。在体内应用后，AuNR 会快速与免疫系统的细胞相互作用。基于其强大的内在吞噬活性，多形核中性粒细胞 (PMN) 特别适合摄取 AuNR 等颗粒物质。因此，了解 AuNR 与 PMN 的相互作用是开发安全有效的治疗应用的关键。在这项研究中，我们研究了 AuNR 在 PMN 中诱导的摄取、细胞内加工和细胞生物学反应。我们表明，AuNRs 的摄取主要通过吞噬作用和巨胞饮作用发生，AuNRs 在 5 分钟内快速沉积在内体中。60分钟内，AuNR 摄取诱导未折叠蛋白反应 (UPR) 以及肌醇需要酶 1 α (IREα) 的诱导和内质网 (ER) 应激的特征。这种早期反应之后是促炎性自分泌激活循环，涉及细胞表面 LOX1 上调和 IL8 和 MMP9 分泌增加。我们的研究为 AuNR 与免疫细胞的相互作用提供了全面的机制洞察，并提出了潜在的目标，以在应用 AuNR 期间限制 PMN 不需要的免疫病理学激活。

更新日期：2022-06-23

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