College of Life Science, Hebei Normal University, Shijiazhuang 050016, Hebei, China; Laboratory of Immunology and Nanomedicine, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055 Shenzhen, China.
Laboratory of Immunology and Nanomedicine, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 518055 Shenzhen, China.
Toxicol Lett. 2022 Oct 1;369:34-42. doi: 10.1016/j.toxlet.2022.08.009. Epub 2022 Aug 31.
The functional activities of gold nanoparticles (AuNPs) on biological systems depend on their physical-chemical properties and their surface functionalizations. Within a biological environment and depending on their surface characteristics, NPs can adsorb biomolecules (mostly proteins) present in the microenvironment, thereby forming a dynamic biomolecular corona on the surface. The presence of this biocorona changes the physical-chemical and functional properties of the NPs and how it interacts with cells. Here, we show that primary human epidermal keratinocytes (HEK) exposed in culture to branched polyethyleneimine (BPEI)-AuNPs, but not to lipoic acid (LA)-AuNPs, show potent particle uptake, decreased cell viability and enhanced production of inflammatory factors, while the presence of a human plasma-derived biocorona decreased NPs uptake and rescued cells from BPEI-AuNP-induced cell death. The mechanistic study revealed that the intracellular oxidative level greatly increased after the BPEI-AuNPs treatment, and the transcriptomic analysis showed that the dominant modulated pathways were related to oxidative stress and an antioxidant response. The stress level measured by flow cytometry also showed a significant decrease in the presence of a biocorona. Further anaylsis discovered that nuclear factor erythroid-2 related factor (Nrf2), a major regulator of anti-oxidant and anti-inflammatory genes, as the key factor related to the AuNPs induced oxidative stress and inflammation. This study provides futher understanding into the mechanisms on how NPs-induced cellular stress and reveals the protective effects of a biocorona on inflammatory responses in HEK at the molecular level, which provides important insights into the biological responses of AuNPs and their biocorona.
金纳米粒子 (AuNPs) 在生物系统中的功能活动取决于它们的物理化学性质和表面功能化。在生物环境中，根据其表面特性，纳米颗粒可以吸附存在于微环境中的生物分子（主要是蛋白质），从而在表面形成动态的生物分子冠。这种生物冠的存在改变了 NPs 的物理化学和功能性质以及它与细胞的相互作用。在这里，我们表明，在培养中暴露于支化聚乙烯亚胺 (BPEI)-AuNPs 的原代人表皮角质形成细胞 (HEK) 表现出强烈的颗粒摄取、细胞活力降低和炎症因子产生增强，而人类血浆衍生的生物冠的存在则减少了 NPs 的摄取并从 BPEI-AuNP 诱导的细胞死亡中拯救了细胞。机制研究表明，BPEI-AuNPs 处理后细胞内氧化水平大大增加，转录组分析表明，主要调节的途径与氧化应激和抗氧化反应有关。在生物冠存在的情况下，通过流式细胞术测量的应激水平也显示出显著下降。进一步分析发现，核因子红细胞 2 相关因子 (Nrf2)，一种主要的抗氧化和抗炎基因调节剂，是与 AuNPs 诱导的氧化应激和炎症相关的关键因素。这项研究进一步了解了 NPs 诱导细胞应激的机制，并揭示了生物冠在 HEK 中分子水平上对炎症反应的保护作用，这为 AuNPs 及其生物冠的生物学反应提供了重要的见解。
