Co-modification with MSC membrane and PDA prevents Fe3O4-induced pulmonary toxicity in mice via AMPK-ULK1 axis

Abstract

Fe₃O₄ nanoparticles are widely used in the diagnosis and treatment of diseases due to their superparamagnetism, but their toxicity in vivo, which can result in apoptosis or autophagy, cannot be ignored. It has been reported that polydopamine (PDA) modification can reduce the toxicity of Fe₃O₄ and increase its biocompatibility. However, more research is warranted to further improve the modification method. We therefore developed a new method to coat Fe₃O₄@PDA nanoparticles with the mesenchymal stem cell membrane (MSCM) and evaluated the toxicity of the modified particles in the lungs of mice. We found that the MSCM modification significantly reduced lung injury induced by Fe₃O₄ particles in mice. Compared with Fe₃O₄@PDA nanoparticles, co-modification with MSCM and PDA significantly reduced autophagy and apoptosis in mouse lung tissue, and reduced activation of autophagy mediated by the AMPK-ULK1 pathway axis. Thus, co-modification with MSCM and PDA prevents Fe₃O₄-induced pulmonary toxicity in mice by inhibiting autophagy, apoptosis, and oxidative stress.

Keywords: Apoptosis; Autophagy; Fe(3)O(4); Mesenchymal stem cells membrane.