Cationic polystyrene nanospheres induce autophagic cell death through the induction of endoplasmic reticulum stress
Cationic polystyrene nanospheres induce autophagic cell death through the induction of endoplasmic reticulum stress
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DOI：
10.1039/c4nr05509h
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发表时间：
2015-01-01
期刊：
影响因子：
6.7
通讯作者：
Wang, Ying-Jan
中科院分区：
文献类型：
--
作者：
Chiu, Hui-Wen;Xia, Tian;Wang, Ying-Jan
纳米颗粒（NPs）已被用于生产广泛的产品，这些产品在医学成像和药物递送中具有应用。由于其化学稳定性，良好控制的尺寸和表面电荷，聚苯乙烯（PS）纳米粒子已被开发为生物传感器和药物递送载体。然而，可能的不良生物学效应和潜在机制仍不清楚。最近，自噬已被牵连在细胞死亡的调节。在这项研究中，我们评估了具有不同表面电荷的PS NPs库。我们发现NH 2标记的聚苯乙烯（NH 2-PS）纳米球具有高毒性，在巨噬细胞（RAW 264.7）和肺上皮细胞（BEAS-2B）中的摄取增强。此外，NH_2-PS还能诱导细胞自噬性死亡。NH 2-PS由于活性氧簇（ROS）的产生和错误折叠蛋白质聚集引起的内质网（ER）应激而增加自噬通量。ER应激的抑制降低了NH 2-PS处理的细胞的细胞毒性和自噬。此外，Akt/mTOR和AMPK信号通路参与了NH 2-PS引发的自噬性细胞死亡的调控。这些结果表明自噬在阳离子NP诱导的细胞死亡中起重要作用，并为抑制毒性和安全材料设计提供了机制见解。
Nanoparticles (NPs) have been used to produce a wide range of products that have applications in imaging and drug delivery in medicine. Due to their chemical stability, well-controlled sizes and surface charges, polystyrene (PS) NPs have been developed as biosensors and drug delivery carriers. However, the possible adverse biological effects and underlying mechanisms are still unclear. Recently, autophagy has been implicated in the regulation of cell death. In this study, we evaluated a library of PS NPs with different surface charges. We found that NH2-labeled polystyrene (NH2-PS) nanospheres were highly toxic with enhanced uptake in macrophage (RAW 264.7) and lung epithelial (BEAS-2B) cells. Furthermore, NH2-PS could induce autophagic cell death. NH2-PS increased autophagic flux due to reactive oxygen species (ROS) generation and endoplasmic reticulum (ER) stress caused by misfolded protein aggregation. The inhibition of ER stress decreased cytotoxicity and autophagy in the NH2-PS-treated cells. In addition, the Akt/mTOR and AMPK signaling pathways were involved in the regulation of NH2-PS-triggered autophagic cell death. These results suggest an important role of autophagy in cationic NP-induced cell death and provide mechanistic insights into the inhibition of the toxicity and safe material design.