Liu Jia, Zheng Liuting, Li Xinyue, Tang Wei, Guo Manyu, Wang Yuxing, Tan Xiaoqi, Chang Jiajia, Zhao Huiyue, Zhu Dongsheng, Ma Yu-Qiang, Huo Da
Department of Pharmaceutics, and Nanjing Medical University, Nanjing 211166, P. R. China.
Department of Medicinal Chemistry, School of Pharmacy, Nanjing Medical University, Nanjing 211166, P. R. China.
ACS Nano. 2025 Feb 11;19(5):5659-5679. doi: 10.1021/acsnano.4c15876. Epub 2025 Jan 30.
Understanding the interaction between nanomaterials and cellular structures is crucial for nanoparticle applications in biomedicine. We have identified a subtype of stress granules, called nanomaterial-provoked stress granules (NSGs), induced by gold nanorods (AuNRs). These NSGs differ from traditional SGs in their physical properties and biological functions. Uptake of AuNRs causes reactive oxygen species accumulation and protein misfolding in the cell, leading to NSG formation. Physically, NSGs have a gel-like core and a liquid-like shell, influenced positively by HSP70 and negatively by HSP90 and the ubiquitin-proteasome system. AuNRs promote NSG assembly by interacting with G3BP1, reducing the energy needed for liquid-liquid phase separation (LLPS). NSGs impact cellular functions by affecting mRNA surveillance and activating Adenosine 5'-monophosphate (AMP)-activated protein kinase signaling, crucial for a cellular stress response. Our study highlights the role of LLPS in nanomaterial metabolism and suggests NSGs as potential targets for drug delivery strategies, advancing the field of nanomedicine.
了解纳米材料与细胞结构之间的相互作用对于纳米颗粒在生物医学中的应用至关重要。我们已经鉴定出一种应激颗粒亚型，称为纳米材料诱发应激颗粒（NSG），它由金纳米棒（AuNR）诱导产生。这些NSG在物理性质和生物学功能上与传统应激颗粒不同。AuNR的摄取会导致细胞内活性氧积累和蛋白质错误折叠，从而导致NSG形成。在物理上，NSG有一个凝胶状核心和一个液体状外壳，受到热休克蛋白70（HSP70）的正向影响，以及热休克蛋白90（HSP90）和泛素-蛋白酶体系统的负向影响。AuNR通过与G3BP1相互作用促进NSG组装，降低液-液相分离（LLPS）所需的能量。NSG通过影响mRNA监测和激活对细胞应激反应至关重要的5'-单磷酸腺苷（AMP）激活的蛋白激酶信号传导来影响细胞功能。我们的研究突出了LLPS在纳米材料代谢中的作用，并表明NSG作为药物递送策略的潜在靶点，推动了纳米医学领域的发展。
