Downregulation of MIM protein inhibits the cellular endocytosis process of magnetic nanoparticles in macrophages

Abstract

Magnetic nanoparticles (MNPs) are widely used in biomedical applications in vivo. However, the endocytosis of mononuclear phagocyte system (MPS) is still a major challenge for MNPs delivery in vivo. MIM (MTSS1) is a multifunctional scaffold protein to regulate both actin dynamics and membrane dynamics, which may decide the readily particles clear ability of MPS and be implicated in the cellular endocytosis. To find out the exact role of MIM plays in the nanoparticle uptake process of macrophages, we established a MIM knock-down cell line RAW 264.7^MIM-. The endocytosis rate and efficiency were detected to find out the differences between the normal RAW 264.7 and RAW 264.7^MIM- cell after 24 h of exposure to the Fe₂O₃@DMSA MNPs (70 nm hydrodynamic size). The results indicated that the clathrin-mediated endocytosis of RAW 264.7^MIM- cell involves fewer particles than normal RAW 264.7 cells with significant differences in the concentration ranging from 100 to 200 μg mL⁻¹. Therefore, knock-down the MIM expression in macrophage would affect the endocytosis process to iron oxide nanoparticles mainly in clathrin-mediated pathway. As a whole, our results presented here illustrated that MIM plays a positive role in the cellular endocytosis process of MNPs, which is a meaningful molecular basis for biomedical applications of nanomaterials.