Research Paper Volume 15, Issue 14 pp 6933—6949

Combined surface functionalization of MSC membrane and PDA inhibits neurotoxicity induced by Fe3O4 in mice based on apoptosis and autophagy through the ASK1/JNK signaling pathway

Yang Li1, *, , Te Liu1,2, *, , Xiuying Li1, , Modi Yang3, , Tianxin Liu4, , Jindian Bao4, , Miao Jiang4, , Lingling Hu4, , Yuzhuo Wang5, , Pu Shao1,3, , Jinlan Jiang1, ,

  • 1 Scientific Research Center, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
  • 2 Yibin Jilin University Research Institute, Jilin University, Yibin, Sichuan, China
  • 3 Department of Orthopeadics, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China
  • 4 Jilin University School of Public Health, Changchun, Jilin, China
  • 5 Department of Orthodontics, School and Hospital of Stomatology, Jilin University, Changchun, Jilin, China
* Equal contribution and share first authorship

Received: March 28, 2023       Accepted: June 23, 2023       Published: July 19, 2023      

https://doi.org/10.18632/aging.204884
How to Cite

Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The extensive utilization of iron oxide nanoparticles in medical and life science domains has led to a substantial rise in both occupational and public exposure to these particles. The potential toxicity of nanoparticles to living organisms, their impact on the environment, and the associated risks to human health have garnered significant attention and come to be a prominent area in contemporary research. The comprehension of the potential toxicity of nanoparticles has emerged as a crucial concern to safeguard human health and facilitate the secure advancement of nanotechnology. As nanocarriers and targeting agents, the biocompatibility of them determines the use scope and application prospects, meanwhile surface modification becomes an important measure to improve the biocompatibility. Three different types of iron oxide nanoparticles (Fe3O4, Fe3O4@PDA and MSCM-Fe3O4@PDA) were injected into mice through the tail veins. The acute neurotoxicity of them in mice was evaluated by measuring the levels of autophagy and apoptosis in the brain tissues. Our data revealed that iron oxide nanoparticles could cause nervous system damage by regulating the ASK1/JNK signaling pathway. Apoptosis and autophagy may play potential roles in this process. Exposure to combined surface functionalization of mesenchymal stem cell membrane and polydopamine showed the neuroprotective effect and may alleviate brain nervous system disorders.

Abbreviations

MSCs: Mesenchymal stem cells; HUMSCs: Human umbilical mesenchymal stem cells; PDA: Polydopamine; NPs: Nanoparticles; ASK1: Apoptosis signal-regulating kinase 1; JNK: c-Jun NH2-terminal kinase; TEM: Transmission electron microscopy; DLS: Dynamic light scattering; SDS-PAGE: Sodium dodecyl sulfate polyacrylamide gel electrophoresis; IL-1β: Interleukin-1β; IL-6: Interleukin-6; IL-10: Interleukin-10; IL-13: Interleukin-13; IFN-γ: Interferon γ; TNF-α: Tumor necrosis factor-α; MIP-2: Macrophage inflammatory protein-2; ROS: Reactive oxygen species; SOD: Superoxide dismutase; MDA: Malondialdehyde; GSH-Px: Glutathione Peroxidase; TUNEL: TdT-mediated dUTP Nick-End Labeling; CXCR4: CXC-chemokine receptor 4; SPIONs: superparamagnetic Fe3O4 nanoparticles; BH3: Bcl-2 homology 3; BAK: Bcl-2 antagonist killer 1; Bax: Bcl-2 associated X; MOMP: Mitochondrial outer membrane permeabilization; MTX: Methotrexate; Al-NPs: Alumina nanoparticles.