Effects Of Fe₃O₄@PDA Nanoparticles-Modified Mesenchymal Stem Cells On AD Model Mice

Alzheimer’s Disease（AD）is a neurodegenerative Disease with insidious onset and progressive progression.The main pathological features of AD are Aβamyloid plaque deposition,Neurofibrillary Tangles（NFT）,and loss of selective neurons and synapses in the cerebral cortex and hippocampus.The occurrence and development of AD are closely related to the deficiency of neurotrophic factors,Ca²⁺channel damage,mitochondrial damage and other factors.Stem cells（SCs）are self-renewing cells with multidirectional differentiation potential.Because of this characteristic,in recent years,the research of stem cell therapy for cancer and nervous system diseases has increased rapidly.In the research of Alzheimer’s disease treatment,the stem cells used as research objects mainly include tissue-specific stem cells,embryonic stem cells and induced pluripotent stem cells.The Stem Cells used in this study are human Umbilical Cord-Mesenchymal Stem Cells（h UC-MSCs）.Compared with other Stem Cells,the advantages of Umbilical cord-mesenchymal Stem Cells are convenient to take materials,free from ethical controversy,characterized by blood-brain barrier permeability,low tumorigenicity,and little immune reaction.Biological Nanoparticle（BNP）is a new multifunctional drug delivery system that combines artificial nano-particles with natural Biological materials and has the advantages of both synthetic system and Biological system.Biological nanomaterials have been widely used in anti-tumor,anti-virus,anti-apoptosis and other fields because of their good biocompatibility,high targeting ability,drug release control ability,improving drug efficacy and reducing toxic and side effects.The Fe3O4@PDA nanoparticles（NPs）used in this study were prepared by preassembled Fe3O4 nanoparticles modified with the outer shell of Polydopamine（PDA）,which has excellent biocompatibility and strong targeting ability under magnetic field.In this study,a mixture of human umbilical cord mesenchymal stem cells and Fe3O4@PDA NPS was injected into APP/PS1△9 transgenic mice via tail vein to evaluate the therapeutic effect of this medicinal products on Alzheimer’s disease model mice.The findings are as follows:In the cell experiments,after Okada Acid（Okadaic Acid,OA）induction of human neuroblastoma（SH-SY5Y）cells after co-culture with h UC-MSCs,cell activity measured by the CCK-8 significantly higher than control group.Western blot experiments further showed that the addition of h UC-MSCs could inhibit Poly-ADP-Ribose Polymerase（PARP）cleavage,hydrolyse Amyloid Protein Precursor（APP）,and restore the expression level of Brain-Derived Neurotrophic Factor（BDNF）.In a mouse model,we first evaluated the targeting ability of Fe3O4@PDA NPs by fluorescence imaging of mice just after injection,and found that the NPs-modified human umbilical cord mesenchymal stem cells were able to target damaged sites more quickly in the model mice.Then,the memory ability of the model mice was evaluated from the perspective of behavior through the water maze test.It was found that the mean escape latency and the final mean latency of the stem cell injection group were better than the control group.Immunohistochemical assay was used to detect the expression of Alzheimer’s disease-related proteins in the brain of mice.It was found that compared with the control mice,the expression levels of Synaptophysin（SYN）and BDNF in the brain of mice injected with stem cell preparation were significantly increased,the expression level of Aβand the abnormal phosphorylation level of Tau protein were decreased.Subsequently,the expression of Alzheimer’s disease-related proteins in the brain of mice was further detected by Western blot assay,and the detection results were consistent with the results of immunohistochemical assay.In conclusion,the injection of human umbilical cord mesenchymal stem cells combined with Fe3O4@PDA NPS can significantly improve the disease condition of Alzheimer’s disease model mice,and the addition of NPS can enhance the ability of stem cells to target damaged sites,thereby improving the therapeutic effect.Therefore,human umbilical cord mesenchymal stem cell-based therapy and the application of Fe3O4@PDA NPS can be used as a new treatment for Alzheimer’s disease,and provide new ideas for drug development of Alzheimer’s disease.