A Biodegradable And Ultrasound Imaging Visible PLGA-Fe₃O₄ Implant For Magnetic-hyperthermia-induced Liver Cancer Eradication

PART ⅠPREPARATION OF PLGA-FE3O4 AND PERFORMANCE EVALUATIONSObjective To prepare injectable and phase transitional magnetocaloric material,and then evaluate physical and magnetocaloric characterizations.Method Three types of PLGA-Fe₃O₄ containing different amounts of Fe₃O₄ powder（1%,10%,and 20%）were developed,and the time of phase transformations were recorded by ultrasound imaging.Solid phase PLGA-Fe₃O₄ were acquired scanning electron microscope.When exposed to AMF,temperature variations were recorded and select the optimum Fe₃O₄ mass fraction of PLGA-Fe₃O₄.Liquid 50μl PLGA-10%Fe₃O₄ were injected into the middle of the excised organization blocks via syringe,and exposed to AMF for 1min,2min,3min,4min,5min,respectively.The coagulative necrosis area after ablation and the temperature variations were recorded.Result PLGA-Fe₃O₄ magnetocaloric material was porous under SEM.PLGA-10%Fe₃O₄ was selected after comparing the coefficients.With the PLGA-10%Fe₃O₄ injection,the 1-5min AMF were applied,the greater volume of tissue coagulation necrosis would be,which provided some appropriate experiment parameters subsequent in vivo experiment.Conclusion PLGA-Fe₃O₄ was an ultrasound-guided,injectable and phase transitional phase transitional material materials,which had great temperature control,as well as,it could generate heat when exposed to AMF,then lead to coagulative necrosis of tissue.The longer exposed to AMF,the wider range of ablation be gotten.PART Ⅱ IN VIVO DEGRADABILITY OF PLGA-FE3O4Objective To explore biosecurity and biodegradability for appropriate dosage of PLGA-Fe₃O₄ magnetocaloric material and value treatment effect.Method PLGA-10%Fe₃O₄ magnetocaloric material was prepared.Then 50μl PLGA-10%Fe₃O₄were injected into subcutaneous tissue of Kunming mice,while equal amount of saline were injected into the control group mice.Photos were recorded after injection,1 month later,2 month later,respectively.The body weight changes of two groups were recorded.After 2 month,HE stain and Prussian stain were used to hearts,livers,spleens,lungs and kidneys of Kunming mice,respectively.Result The PLGA-10%Fe₃O₄ implant were metabolized with spleen and liver after injection 2 month as well as KM mice were in good health condition.The heart,liver,spleen,lung and kidney were no difference with normal tissues.Conclusion The PLGA-Fe₃O₄ phase transitional magnetocaloric material had excellent biodegradability,biocompatibility and biosafty.PART Ⅲ ULTRASOUND IMAGING VISIBLE PLGA-FE3O4 IMPLANT FOR MAGNETIC-HYPERTHERMIA-INDUCED LIVER CANCER ERADICATIONObjective To prepare injectable and phase transitional PLGA-Fe₃O₄ magnetocaloric material for magnetic hyperthermia SMMC-7721 liver cancer,and to explore in vivo ultrasound imaging with CT double modal imaging.Method With reference to the above-mentioned results,under the guidance of ultrasound,injected 50 μl PLGA-Fe₃O₄ into tumor,then gave it to micro-CT examination and AMF was applied for 3min.All of the remaining mice were fed for further observation of tumor growth.The tumor volume and body weight were recorded daily.Result The implant phase transition were observed by ultrasound imaging and micro-CT imaging showed high density of materials.In the observation of tumor growth,the tumors of treatment group grew well with time.The ablated tumors fell off at the 2nd day after treatment and then gradually healed at about 15 days after treatment without surrounding tissue damage.Conclusion A biodegradable and ultrasound imaging visible PLGAFe₃O₄ magnetocaloric material combined with alternating magnetic field are able to ablate liver cancer and process of ultrasound and CT double modal imaging.