Superparamagnetic Chitosan Loaded With IGFBP₅ Nanoparticles In The Targeted Treatment Of Lung Metastasis Of Osteosarcoma

Purpose:In this study,Superparamagnetic Chitosan Nanoparticles（SPCIONPs）,was prepared study its effectiveness and its biological safety as gene carriers,and magnetic transfection system was used to targetedly treat the lung metastasis of osteosarcoma.Methods:SPCIONPs was characterized by Transmission Electron Microscope,Fourier Transform Infrared Spectroscopy,Superconducting Quantum Interferometer and Atomic Force Microscope.CCK8,HE staining of heart,liver,spleen,lung and kidney and blood biochemical indexes were used to detect its biosafety in vivo and in vitro.Confocal laser microscope was used to detect the transfection in vitro;colony formation was used to detect the SPCIONPs/IGFBP₅ on cell proliferation,the wound healing assay was used to detect SPCIONPs/IGFBP₅ on cell migration,and the transwell assay was used to detect the SPCIONPs/pIGFBP₅ on cell invasion;In vivo experiments,prussian blue,and HE staining of lung tissue were used to detect nebulized inhalation of SPCIONPs/pIGFBP₅ and targeted the lung metastasis of osteosarcoma with the aid of an external magnetic field.Results:The results of FTIR and AFM showed that the carboxylated superparamagnetic iron oxide and chitosan were successfully grafted in the form of amide bonds.The average particle size of the prepared SPCIONPs was about 22 nm,and the Zeta potential was 11.3 m V.The results of gel electrophoresis showed that SPCIONPs can bind tightly to plasmids and protect them from DNase degradation;CCK8,in vivo heart,liver,spleen,lung and kidney HE staining,blood routine,CRP and liver and kidney function results showed that it exhibited no obvious inflammatory response in vivo and in vitro.The ratio difference was not statistically significant compared to the control proup;the transfection in vitro showed that the SPCIONPs/pIGFBP₅ group had more red fluorescence expression than the chitosan loaded IGFBP₅（CS/pIGFBP₅）group.In vitro malignant biological results showed that SPCIONPs/pIGFBP₅ could significantly inhibit cell proliferation,cell migration and invasion.With the assistance of external magnetic field,the prussian blue staining of tissue sections showed that there were a large number of blue particles deposited in the lung,and HE staining of lung tissue in vivo showed that the number of lung metastases in the SPCIONPs/pIGFBP₅ group was less than that in the control group.Conclusion:In conclusion,the prepared SPCIONPs has good biosafety,can effectively transfer pIGFBP₅ into 143B cells,and can target the treatment of osteosarcoma lung metastasis under the action of external magnetic field.