Inorganic Nanomaterials as Highly Efficient Inhibitors of Cellular Hepatic Fibrosis

Chronic liver dysfunction usually begins with hepatic fibrosis. To date, no effective anti-fibrotic drugs have been approved for clinical use in humans. In the current work, titanium dioxide (TiO₂) nanoparticles (NPs) and silicon dioxide (SiO₂) NPs are used as active inhibitors with intrinsic chemico-physico properties to block fibrosis and the associated phenotypes through acting on hepatic stellate cells (HSCs, the liver machinery for depositing scar tissues seen in fibrosis). Using LX-2 cells as the HSC model, internalized nanomaterials are found to suppress classical outcomes of cellular fibrosis, for example, inhibiting the expression of collagen I (Col-I) and alpha smooth muscle actin (α-SMA), initiated by transforming growth factor β (TGF-β)-activated HSCs in both a concentration-dependent and a time-dependent manner. Biochemically, these nanomaterials could also facilitate the proteolytic breakdown of collagen by up-regulation of matrix metalloproteinases (MMPs) and down-regulation of tissue inhibitors of MMPs (TIMPs). Furthermore, through regulating epithelial-mesenchymal transition (EMT) genes [e.g., E-cadherin (E-Cad) and N-cadherin (N-Cad)], the adhesion and migration profiles of TGF-β-activated LX-2 cells treated with nanomaterials were further inhibited, reverting them to a more quiescent state. Thus, the collective results pave the new way that nanomaterials can be used as potential therapeutic inhibitors for the treatment of in vivo fibrosis.