PLGA-NdFeB-Fe3O4 implant for magnetic hyperthermia of mice bearing breast cancer / 中国介入影像与治疗学

ABSTRACT

Objective To prepare a novel loaded NdFeB and Fe3O4 liquid-solid phase inversion poly (polylactic-co-glycolic acid,PLGA) in situ implant (PLGA 60％ NdFeB-20％ Fe3O4) for ultrasound-guided intratumoral injection,and to investigate its intensity of magnetism and therapeutic efficiency of nude mice bearing MDA-MB-231 breast cancer.Methods PLGA-60 ％ NdFeB-20 ％ Fe3O4 in situ implant was prepared.The microstructure of PLGA-60 ％ NdFeB-20 ％ Fe3O4 was tested with scanning electron microscope (SEM).Magnetometer was used to qualify the intensity of magnetism.For the in vitro assay,60 μl solid PLGA-60％ NdFeB-20％ Fe3O4 implant was put in the center of the electromagnetic induction heating coil.Infrared thermal video of the tubes was simultaneously recorded.The size of 2 cm × 2 cm× 2 cm fresh ex vivo bovine liver was prepared,and then 60 μl PLGA-60％ NdFeB-20％ Fe3O4 was injected into it.Similarly,ex vivo bovine liver was heated by the above intermittent time for 1,2,3,4 minutes,respectively,and the ablation volume was calculated.Finally,nude mice were equally divided into treatment group and control group.Mice in treatment group were discontinuously heated for 3 min after being injected with the above mentioned implant,while CEUS was performed before and after heating to observe the blood perfusion in the tumor.One nude mouse was executed on the next day in each group,then pathological sections and HE staining of tumor tissue were taken,whereas the growth of the remaining nude mice were observed daily.Results SEM showed the implant with rough and porous surface.The magnetism increased with the volume of material.The tube and bovine liver experiments showed that the PLGA-60 ％ NdFeB-20％ Fe3O4 generated heat efficiently.The bovine liver ablation experiment showed that the range of ablation of 60 μl PLGA-60 ％ NdFeB-20％ Fe3O4 implant reached (2.34±0.25)cm3 after 3 min heating.In vivo experiments showed that the tumor tissue began to form a scab on the 2nd day,and the scab began to desquamate on the 20th day.CEUS showed the original predominant enhancement disappeared significantly after the treatment.HE staining proved that cancer cells had coagulative necrosis,whereas tumors in control group became bigger.Conclusion PLGA-60％ NdFeB-20％ Fe3O4 in situ implant can produce obvious thermal effect under high frequency alternating magnetic field,therefore can be effectively ablated with nude mice MDA-MB-231 breast cancer during time interval heating.