The Potential Application of Magnetic Nanoparticles for Liver Fibrosis Theranostics

Abstract

Liver fibrosis is a major cause of morbidity and mortality worldwide due to chronic liver damage and leading to cirrhosis, liver cancer, and liver failure. To date, there is no effective and specific therapy for patients with hepatic fibrosis. As a result of their various advantages such as biocompatibility, imaging contrast ability, improved tissue penetration, and superparamagnetic properties, magnetic nanoparticles have a great potential for diagnosis and therapy in various liver diseases including fibrosis. In this review, we focus on the molecular mechanisms and important factors for hepatic fibrosis and on potential magnetic nanoparticles-based therapeutics. New strategies for the diagnosis of liver fibrosis are also discussed, with a summary of the challenges and perspectives in the translational application of magnetic nanoparticles from bench to bedside.

Keywords: drug delivery; liver fibrosis; magnetic nanoparticles; nanomedicine; theranostics.

FIGURE 1

Inflammation in fibrosis. The inflammatory response could be induced by hepatocyte damage leading to the activation of macrophages and to a production of ROS and TGF-β1 and to the differentiation of quiescent HSCs in MFBs which in turn may trigger liver fibrosis.

FIGURE 2

Medical applications of SPION-based MRI in liver, cardiovascular, inflammation, gastrointestinal tract, CNS, and tumor imaging (A). Application of SPION‐labeled stem cells as a monitoring regenerative therapy in tracking of stem cells after transplantation (B). Reproduced with permission (Sharifi et al., 2015) Copyright 2015, Wiley.

FIGURE 3

Comparison of pre- and post-contrast in vivo MRI of the liver in a region of interest from fibrosed areas (above) and in colorized images of the original MRI (below) after 10 min of application of citrate-coated ultrasmall SPIONs (A). The graph of pixel intensity in pre- and post-contrast of liver is presented in (B). Reproduced with permission (Saraswathy et al., 2014) Copyright 2014, Elsevier B.V.

FIGURE 4

Effects of FGF-2-conjugated SPIONs on HSC activation in vitro and in vivo. (A) Immunofluorescent detection of type-I collagen in control and TGF-β-stimulated LX2 cells in control, FGF-2-, FGF-2-SPION-, or SPION-treated groups. (B) Expression levels of a-SMA and type-I collagen in control, FGF-2-, FGF-2-SPION-, or SPION-treated groups. (C) Western-blot analysis of type-I collagen, pAkt, Akt, a-SMA, and ß-actin in control, FGF-2-, FGF-2-SPION-, or SPION-treated groups. (D) Quantitative analysis of Western-blot results. Reproduced under the terms and conditions of the Creative Commons Attribution 4.0 International License (Kurniawan et al., 2020). Copyright 2020, Elsevier.

FIGURE 5

The role of engineered Relaxin in the treatment and diagnosis of liver cirrhosis. Reproduced with permission (Nagórniewicz et al., 2019). Copyright 2019, Elsevier Inc.