Inorganic Nanomaterials as Highly Efficient Inhibitors of Cellular Hepatic Fibrosis

Abstract

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 (TiO) nanoparticles (NPs) and silicon dioxide (SiO) 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.

Nanomaterials as Inhibitors of Epithelial Mesenchymal Transition in Cancer Treatment

“…In particular, TiO 2 NPs induce lysosomal degradation of the TGFβ receptor complex (TβRI/II), and thereby downregulate the expression of TGFβ-target genes. TiO 2 NPs and silicon dioxide (SiO 2 NPs) were able to suppress ECM production, blocking the effect of TGFβ in cells implicated in liver fibrosis [55].…”

Functionalizing NaGdF4:Yb,Er Upconverting Nanoparticles with Bone-Targeting Phosphonate Ligands: Imaging and In Vivo Biodistribution

“…Although further studies are required, we speculate that phosphonate-capped UCNPs can escape the endothelium and reach the skeleton via a mechanism known as nanomaterial induced endothelial leakiness. In this process, nanomaterials enter and enlarge the nanosized gaps between microvascular capillary endothelial cells favouring their leakage to other tissue sites [29,30].…”

Photostable and Biocompatible Fluorescent Silicon Nanoparticles for Imaging-Guided Co-Delivery of siRNA and Doxorubicin to Drug-Resistant Cancer Cells

“…The results demonstrate the effectiveness of fluorescent SiNPs for the imaging-guided co-delivery of siRNA and DOX for therapy of MCF-7/ADR cells, and pave the way for the development of nanomedicines for MDR cancer cells. Of note, although silicon is distinguished by its low-or non-toxicity, numerous pioneering studies conducted by Professor Leong have revealed that nanoparticles may induce endothelial leakiness [37][38][39][40]. Therefore, further understanding of the behavior of SiNPs and SiNP-DOX/siRNA nanocomposites in vivo requires further investigation for their potential clinical application.…”