Synthesis Of Novel Ferrimagnetic Iron Oxide Nanoparticles And Its Application For Efficient Gene Delivery On Mesenchymal Stem Cells

Objective:The present study aims to synthesize novel ferrimagnetic iron oxide nanoparticles(MFIONs)which have a good water dispersity and explore its potential for the gene modification on mesenchymal stem cells(MSCs),as well as the therapy efficacy of MFIONs modified MSCs on ischemic stroke.Method:1.Iron oxide nanocubes were firstly synthesized by the "heat up" method,and MFIONs were further obtained after surface modification of double layer oleic acid and the hydrophilic group PEI.Characterization was then carried out by transmission electron microscope,fourier transform infrared spectroscopy,thermogravimetric analysis and hysteresis loop.2.Taken MFIONs as the inner core,DNA and PEI as the outer layers,layer by layer assembly method was applied for the construction of MFIONs gene complexes.The best transfection condition was explored and applied for gene modification on MSCs.3.By comparing with the gene complexes based on superparamagnetic iron oxide nanoparticles(SPIONs),the transfection mechanism of MFIONs was explored and the relation between transfection mechanism and properties of nanocarriers was also investigated.4.Brain derived neurotrophic factor(BDNF)secretion capacity of MFIONs modified MSCs with BDNF-encoded plasmid was investigated,and the therapy efficacy on ischemic stroke mice in vivo was also evaluated by modified neurological severity score(mNSS)and TTC staining.Results:1.Uniform iron oxide nanocubes with a size of 25 nm were successfully synthesized.The MFIONs with a good water dispersity and nanochains were further obtained after the surface modification.2.MFIONs gene complexes were successfully constructed,and were further applied on the gene modification of MSCs.The best transfection condition was MFIONs for 30 ?g/mL while N/P ratio for 10.And an efficient gene transfection efficiency was achieved even without the assistant of external magnetic field,it was 10 times higher than PEI.Besides,MFIONs had a good biocompatibility.3.The self-assembled nanochains assisted MFIONs gene complexes for achieving a higher endocytosis and gene transfection efficiency.4.MFIONs modified MSCs could promote the expression of BDNF.Moreover,MFIONs modified MSCs had the best therapy efficacy in the treatment of ischemic stroke mice since the mNSS score demonstrated a good recovery of neurologic functions while the survival rate was improved significantly and the smallest ischemic area was observed by TTC.Conclusion:MFIONs with nanochains could be endocytosed efficiently by MSCs,leading to an efficient and safe modification of MSCs.Carried with BDNF-encoded plasmid,MFIONs modified MSCs had the best secretion capacity,and demonstrated a good potential for the treatment of ischemic stroke.