Cationic polystyrene nanospheres induce autophagic cell death through the induction of endoplasmic reticulum stress

被引:185
作者
Chiu, Hui-Wen [1 ,5 ,6 ]
Xia, Tian [2 ]
Lee, Yu-Hsuan [1 ]
Chen, Chun-Wan [3 ]
Tsai, Jui-Chen [4 ]
Wang, Ying-Jan [1 ,7 ,8 ]
机构
[1] Natl Cheng Kung Univ, Dept Environm & Occupat Hlth, Tainan 70101, Taiwan
[2] Univ Calif Los Angeles, Dept Med, Div NanoMed, Los Angeles, CA 90024 USA
[3] Minist Labor, Inst Labor Occupat Safety & Hlth, Yuan, Taiwan
[4] Natl Cheng Kung Univ, Inst Clin Pharm & Pharmaceut Sci, Tainan, Taiwan
[5] Taipei Med Univ, Dept Internal Med, Shuang Ho Hosp, Div Nephrol, Taipei, Taiwan
[6] Taipei Med Univ, Grad Inst Clin Med, Taipei, Taiwan
[7] Asia Univ, Dept Biomed Informat, Taichung, Taiwan
[8] China Med Univ, China Med Univ Hosp, Dept Med Res, Taichung, Taiwan
关键词
CERIUM DIOXIDE NANOPARTICLES; UBIQUITIN-PROTEASOME SYSTEM; ERK1/2 SIGNALING PATHWAYS; UNFOLDED PROTEIN RESPONSE; CANCER-CELLS; ER STRESS; QUANTUM DOTS; IN-VITRO; APOPTOSIS; ACTIVATION;
D O I
10.1039/c4nr05509h
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
收藏
页码:736 / 746
页数:11
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