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 (Bi(2)S(3)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 Bi(2)S(3)NPs with different shapes (Bi(2)S(3)nano rods (BSNR), hollow microsphere Bi(2)S(3)NPs (BSHS) and urchin-like hollow microsphere Bi(2)S(3)NPs (ULBSHS)) were used to evaluatecytotoxicity, autophagy induction, cell migration and invasion in human hepatocellular carcinoma cells (HepG2). Results showed that all three Bi(2)S(3)NPs lead to blockage in autophagic flux, causing p62 protein accumulation. The cell death caused by these Bi(2)S(3)NPs is proved to be autophagy related, rather than related to apoptosis. Moreover, Bi(2)S(3)NPs can reduce the migration and invasion in HepG2 cells in an autophagy-dependent manner. ULBSHS is the most cytotoxic among three Bi(2)S(3)NPs and has the best tumor metastasis suppression. These results demonstrated that, even with relatively low toxicity of Bi(2)S(3)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.