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

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.