Functional Evaluation of 3D Liver Models Labeled with Polysaccharide Functionalized Magnetic Nanoparticles

Abstract

Establishing a rapid in vitro evaluation system for drug screening is essential for the development of new drugs. To reproduce tissues/organs with functions closer to living organisms, in vitro three-dimensional (3D) culture evaluation using microfabrication technology has been reported in recent years. Culture on patterned substrates with controlled hydrophilic and hydrophobic regions (Cell-ableTM) can create 3D liver models (miniature livers) with liver-specific Disse luminal structures and functions. MRI contrast agents are widely used as safe and minimally invasive diagnostic methods. We focused on anionic polysaccharide magnetic iron oxide nanoparticles (Resovist®) and synthesized the four types of nanoparticle derivatives with different properties. Cationic nanoparticles (TMADM) can be used to label target cells in a short time and have been successfully visualized in vivo. In this study, we examined the morphology of various nanoparticles. The morphology of various nanoparticles showed relatively smooth-edged spherical shapes. As 3D liver models, we prepared primary hepatocyte–endothelial cell heterospheroids. The toxicity, CYP3A, and albumin secretory capacity were evaluated in the heterospheroids labeled with various nanoparticles. As the culture period progressed, the heterospheroids labeled with anionic and cationic nanoparticles showed lower liver function than non-labeled heterospheroids. In the future, there is a need to improve the method of creation of artificial 3D liver or to design a low-invasive MRI contrast agent to label the artificial 3D liver.

Biological Scaffolds Assembled with Magnetic Nanoparticles for Bone Tissue Engineering: A Review

“…It is worth mentioning that SPIONs are often used as magnetic resonance imaging (MRI) probes for the imaging, detection, and diagnosis of bone-related diseases and can help to image early bone turnover changes such as osteoarthritis [ 31 , 32 , 33 , 34 ]. Due to the important properties of SPIONs, such as their good biocompatibility and superparamagnetic behavior, they have become an excellent choice for magnetic thermo-therapy and as a magnetic resonance imaging contrast agent [ 27 , 35 , 36 , 37 , 38 , 39 , 40 ]. Magnetic scaffolds can promote bone repair and regeneration via magnetic force, attracting and absorbing growth factors, stem cells, or other biological agents that combine with magnetic ions [ 20 , 41 , 42 ].…”