Autophagic blockage by bismuth sulfide nanoparticles inhibits migration and invasion of HepG2 cells

硫化铋纳米粒子阻断自噬抑制HepG2细胞迁移和侵袭

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作者:Bai-Mei Hao, Ya-Nan Liu, Chen-Yang Zhang, Guang-Qi Li, Wan-Ni Wang, Wei-Dong Xu, Zheng-Bao Zha, Feng Wang, Chao Li, Zhao-Hua Miao, Xiao-Xiao Yang, Yuan-Li Chen, Hai-Sheng Qian, Wei Zhou

Abstract

The biological effects of nanoparticles are of great importance for the in-depth understanding of safety issues in biomedical applications. Induction of autophagy is a cellular response after nanoparticle exposure. Bismuth sulfide nanoparticles (Bi2S3 NPs) are often used as a CT contrast agent because of their excellent photoelectric conversion ability. Yet there has been no previous detailed study other than a cell toxicity assessment. In this study, three types of Bi2S3 NPs with different shapes (Bi2S3 nano rods (BSNR), hollow microsphere Bi2S3 NPs (BSHS) and urchin-like hollow microsphere Bi2S3 NPs (ULBSHS)) were used to evaluatecytotoxicity, autophagy induction, cell migration and invasion in human hepatocellular carcinoma cells (HepG2). Results showed that all three Bi2S3 NPs lead to blockage in autophagic flux, causing p62 protein accumulation. The cell death caused by these Bi2S3 NPs is proved to be autophagy related, rather than related to apoptosis. Moreover, Bi2S3 NPs can reduce the migration and invasion in HepG2 cells in an autophagy-dependent manner. ULBSHS is the most cytotoxic among three Bi2S3 NPs and has the best tumor metastasis suppression. These results demonstrated that, even with relatively low toxicity of Bi2S3 NPs, autophagy blockage may still substantially influence cell fate and thus significantly impact their biomedical applications, and that surface topography is a key factor regulating their biological response.

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