An Experimental Study Of Targeted Tumor Therapy Using Magnetic Nanoparticles Loaded IL-2

Objective:1To prepare magnetic nanoparticles loaded IL-2(IL-2-Fe3O4-PLGA) which has the function of controlled release and targeting ability in immunotherapy for tumor.2To observe the antitumor effect and the targeted accumulation of tumor tissue of magnetic nanoparticles loaded IL-2with an external magnetic field in S180sarcoma mice model.Methods:Part11.1IL-2-Fe3O4-PLGA was generated by double emulsion-solvent evaporation method.The morphology and size of IL-2-Fe3O4-PLGA were observed by scanning electron microscope(SEM) and laser particle size analyzer.1.2IL-2-Fe3O4-PLGA encapsulation rate and drug releasing characteristics in vitro were measured with enzyme linked immunosorbent assay (ELISA Kit).1.3The biological activity of the released IL-2was evaluated by MTT assay.Part22.1In vivo,fifty BALB/c female mice with implanted tumor of S180sarcoma cells were randomly divided into five groups:①treating group with IL-2-Fe3O4-PLGA combining outside magnectic field②treating group with IL-2-Fe3O4-PLGA③treating group with Fe3O4-PLGA④treating group with free IL-2⑤control group with saline. And the tumor growth and survival time of the mice were observed.2.2Pathological analysis:Prussian blue staining and HE showed the accumulation of IL-2-Fe3O4-PLGA in the tumor tissue.Results:Part11.1The size of IL-2-Fe3O4-PLGA ranges from150to2000nm.And the magnetic nanoparticles were spherical with mean diameter697.6±0.51nm. The loading efficiency and encapsulation rate of magnetic nanoparticles loaded IL-2were [(6.93±0.17)×10-3]%and83.76±2.12%.1.2In the drug release test in vitro,the cumulative concentration of released IL-2was180ng/ml during15days.(3) MTT method showed that the absorbance value IL-2-Fe3O4-PLGA increased significantly (P<0.05), compared to blank control group.But the difference was not statistically significant (P>0.05),compared to free IL-2group. These results showed IL-2-Fe3O4-PLGA can stimulate lymphocyte proliferation and the released IL-2remained its original activity during the release period.Part22.1Compared to other groups, the tumor size of the group with IL-2-Fe3O4-PLGA combining outside magnectic field decreased, but there was no difference (P>0.05). The survival rate of the bearing tumor mice were no significant differences between the treated groups.2.2(1)Prussian blue stain showed the accumulation of blue particles in the tumor tissue in the group with IL-2-Fe3O4-PLGA combining outside magnectic field.(2)HE staining showed inflammatory cells are clustered in the tumor tissues in the group with IL-2-Fe3O4-PLGA combining outside magnectic field.Conclusion:1Magnetic nanoparticles loaded IL-2were prepared successfully, which has the function of controlled release and targeting ability.They still remain their original activity.2The treating group with IL-2-Fe3O4-PLGA combining outside magnectic field can accumulate the tumor tissue in vivo,which provides a new therapeutic stragey for tumor targeting therapy.