Mesenchymal Stem Cells Labeled With Fluorescent Magnetic Nanoparticles For Targeted Imaging And Hyperthermia Therapy Of Lung Cancer

Objective:To study therapeutic effects of fluorescent magnetic nanoparticles labeled mesenchymal stem cells(FMNP-MSC)for lung cancer A549 in vitro and hyperthermia induced by an alternating magnetic field on lung cancer A549 in nude mice.Methods:The fluorescent magnetic nanoparticles(FMNP)was prepared and characterized,and then were used to label mouse mesenchymal stem cells(MSCs)in vitro,Lung cancer A549 cell was cultured with FMNP-MSC in transwell coculture,morphologic changes of cell,cell cycle and aposptosis,invasion inhibition,expression of CXCR4 and CCR7 were assayed by light and fluorescence microscope,flow cytometry,transwell invasion experiment and Western blot test.The FMNPs-labeled MSCs were injected via tail vein into nude mice bearing non-small cell lung cancer A549 cells,which were followed using small animal fluorescence imaging system and magnetic resonance imaging system.The subcutaneous lung cancer tissues in the nude mice models were subsequently treated in external alternating magnetic field once a week for four weeks,temperature of tumor was detected by optical fiber.Four weeks after treatment,the tumor were collected after euthanizing the animals.Pathology change of tumor tissue was detected by light and fluorescence microscope,cell apoptosis proteins(Bax,Caspase-3)and anti-apoptotic protein(Bcl-2)were detected by Western blot.Results:The average diameter FMNP approximately 40 to 50 nm,with strong progressive,Toxicity of FMNP-MSC is low with a certain concentration(<100 ug/mL),FMNP could accurately into the MSC cells.The proliferation of human being carcinoma A549 cell was increasingly inhitibited,the apoptotic of lung cancer A549 cells were observed and the cycle of lung cancer A549 cells were inhibiteded in the stage G1.In vivo experiments confirmed that MSC FMNP can be carried to the tumor area.Temperature of tumor can heat up to 53? under alternating magnetic field.FNMP-MSC thermal therapy group mice tumor volume and weight growth was significantly inhibited,FMNP-MSC group of mice with tumor volume growth is restrained,the weight was not significantly inhibited.Apoptosis and necrosis change of tumor tissue could be detected by light microscope.Western blot confirmed,Bax protein expression in two treatment group obviously,and Caspase 3,the Bcl-2 in the two treatment groups have no significant expression.Conclusion:In vitro,the diameter of FMNP particle diameter is about 40 to 50 nm,with the characteristics of strong paramagnetism.FMNP-MSC can significantly inhibited A549 lung cancer cell proliferation,induced apoptosis,arrest the cell cycle,reduce the invasion ability.In vivo,FMNP-MSC can accurately targeting to the tumor area,which heat up to the effective temperature under alternating magnetic field,the growth of tumor in mice was significantly inhibited;apoptosis and necrosis could be seen in tumor,may be achieved by increasing the expression of Bax.